In [1]:
import os
import re
In [2]:
import numpy as np
from scipy.sparse.csgraph import shortest_path
import pandas as pd
In [3]:
pd.options.display.max_colwidth=500
In [4]:
ent_pattern = re.compile('T(\d+)\t([A-Z_]+) (\d+ \d+(;\d+ \d+)*)\t(.+)')
rel_pattern = re.compile('R(\d+)\t([A-Z_]+) Arg1:T(\d+) Arg2:T(\d+)')
ref_pattern = re.compile('R(\d+)\tCOREFERENCE Arg1:T(\d+) Arg2:T(\d+)')

folder = './test/sample/'

for filename in os.listdir(folder):
    if filename.endswith('.ann'):
        with open(folder + filename, 'r', encoding='utf8') as fin:
            text = fin.read()

        rels = rel_pattern.findall(text)
        if len(rels) == 0:
            continue
        assert len(rels) == int(rels[-1][0])

        df_ent = pd.DataFrame([(e[0], e[1], e[2], e[4]) for e in ent_pattern.findall(text)], 
                  columns=['id', 'type', 'range', 'text']).set_index('id')
        df_ref = pd.DataFrame(ref_pattern.findall(text), columns=['id', 'ent1', 'ent2'])
        df = df_ref.join(df_ent, on='ent1', rsuffix='1').join(df_ent, on='ent2', rsuffix='2')
        
        common_span = set(df['range']) & set(df['range2'])
        if len(common_span) != 0:
            print(filename)
            display(df)

            coref_dict = {r:e for e, r in zip(df['ent1'], df['range'])}
            ent_dict = {r:e for e, r in zip(df['ent2'], df['range2'])}

            all_spans = sorted(set(df['range']) | set(df['range2']))
            num_spans = len(all_spans)

            df_graph = pd.DataFrame(np.zeros((num_spans, num_spans), dtype=int), index=all_spans, columns=all_spans)

            for r1, r2 in zip(df['range'], df['range2']):
                df_graph.loc[r1, r2] = 1

            d = shortest_path(df_graph.values, directed=True)

            print('new rels')
            new_rels = []
            for e1, e2 in zip(*np.where(((~np.isinf(d)) & (d>1)))):
                r1 = all_spans[e1]
                r2 = all_spans[e2]
                new_rels.append((coref_dict[r1], ent_dict[r2]))

            with open(folder + filename, 'a', encoding='utf8') as fout:
                for i, (e1, e2) in enumerate(new_rels, start=len(rels)+1):
                    rel_str = 'R%d\tCOREFERENCE Arg1:T%s Arg2:T%s'%(i, e1, e2)
                    print(rel_str)
                    fout.write(rel_str + '\n')                        

0001.ann
id ent1 ent2 type range text type2 range2 text2
0 11 18 1 COREFERENCE 701 802 400 mg (88%) of [5-(2,3-difluorophenyl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetic acid ENTITY 6 91 [5-(2,3-difluorophenyl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetic acid
1 12 13 12 COREFERENCE 830 843 a white solid ENTITY 701 802 400 mg (88%) of [5-(2,3-difluorophenyl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetic acid 
new rels
R13	COREFERENCE Arg1:T13 Arg2:T1
0002.ann
id ent1 ent2 type range text type2 range2 text2
0 5 7 4 COREFERENCE 601 612 the solvent ENTITY 367 395 ethanol (20 mL)/water (5 mL)
1 7 9 8 COREFERENCE 691 703 yellow solid ENTITY 614 632;671 687 The title compound (1.180 g, 95.2%)
2 8 13 1 COREFERENCE 614 632;671 687 The title compound (1.180 g, 95.2%) ENTITY 22 139 N-(3-chloro-4-fluorophenyl)-N-(2-fluoro-4-(hydrazinecarbonyl)benzyl)tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 
new rels
R9	COREFERENCE Arg1:T9 Arg2:T1
0003.ann
id ent1 ent2 type range text type2 range2 text2
0 6 15 8 COREFERENCE 451 460 The solid ENTITY 442 449 a solid
1 9 16 2 COREFERENCE 518 550 the title compound (72 mg, 62 %) ENTITY 111 116 LXXVI
2 10 17 1 COREFERENCE 111 116 LXXVI ENTITY 30 109 2'-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3'-fluoro-[2,4'-bipyridin]-5-ol 
new rels
R11	COREFERENCE Arg1:T16 Arg2:T1
0006.ann
id ent1 ent2 type range text type2 range2 text2
0 5 7 4 COREFERENCE 520 531 the solvent ENTITY 294 309 ethanol (10 mL)
1 10 12 11 COREFERENCE 720 732 a foam solid ENTITY 681 716 the title compound (0.115 g, 95.8%)
2 11 17 1 COREFERENCE 681 716 the title compound (0.115 g, 95.8%) ENTITY 22 109 N-((5-(hydrazinecarbonyl)pyridin-2-yl)methyl)-1-methyl-N-phenylpiperidine-4-carboxamide 
new rels
R12	COREFERENCE Arg1:T12 Arg2:T1
0007.ann
id ent1 ent2 type range text type2 range2 text2
0 19 33 20 COREFERENCE 1268 1293 the compound of Example 8 ENTITY 1126 1239 1-(4-(dimethylamino)piperidin-1-yl)-3-(1-ethyl-1H-imidazol-2-yl)-3-hydroxypropan-1-one (0.221 g, 0.751 mmol, 43%)
1 20 22 21 COREFERENCE 1298 1313 a colorless oil ENTITY 1268 1293 the compound of Example 8
2 21 32 1 COREFERENCE 1126 1239 1-(4-(dimethylamino)piperidin-1-yl)-3-(1-ethyl-1H-imidazol-2-yl)-3-hydroxypropan-1-one (0.221 g, 0.751 mmol, 43%) ENTITY 25 111 1-(4-(dimethylamino)piperidin-1-yl)-3-(1-ethyl-1H-imidazol-2-yl)-3-hydroxypropan-1-one 
new rels
R22	COREFERENCE Arg1:T33 Arg2:T1
R23	COREFERENCE Arg1:T22 Arg2:T20
R24	COREFERENCE Arg1:T22 Arg2:T1
0008.ann
id ent1 ent2 type range text type2 range2 text2
0 3 6 2 COREFERENCE 229 232 87% ENTITY 48 69 12.12 g of Compound 7
1 4 7 1 COREFERENCE 48 69 12.12 g of Compound 7 ENTITY 37 47 Compound 7 
new rels
R5	COREFERENCE Arg1:T6 Arg2:T1
0009.ann
id ent1 ent2 type range text type2 range2 text2
0 5 7 5 COREFERENCE 251 262 the solvent ENTITY 149 160 DMF (14 mL)
1 7 15 9 COREFERENCE 382 388 eluent ENTITY 360 378 CH2Cl2/MeOH (10:1)
2 10 12 11 COREFERENCE 415 434 a light brown solid ENTITY 397 411;435 450 the product 34 (273 mg, 76.4%)
3 11 17 1 COREFERENCE 397 411;435 450 the product 34 (273 mg, 76.4%) ENTITY 13 24 Compound 34 
new rels
R12	COREFERENCE Arg1:T12 Arg2:T1
0010.ann
id ent1 ent2 type range text type2 range2 text2
0 1 18 1 COREFERENCE 114 124 compound 7 ENTITY 10 112 N-(2-Methoxy-4-(piperidin-4-yl)phenyl)-3-(2-methoxyphenyl)-3H-[1,2,3]tria zolo[4,5-d]pyrimidin-5-amine
1 4 19 6 COREFERENCE 398 410 the solution ENTITY 259 280 the reaction solution
2 14 17 16 COREFERENCE 814 826 This product ENTITY 774 812 a yellow solid 7-c (6.9 g, yield: 82%)
3 15 24 3 COREFERENCE 774 812 a yellow solid 7-c (6.9 g, yield: 82%) ENTITY 141 153 compound 7-c 
new rels
R16	COREFERENCE Arg1:T17 Arg2:T3
0011.ann
id ent1 ent2 type range text type2 range2 text2
0 1 15 1 COREFERENCE 16 85 7-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one ENTITY 0 14 Intermediate 5
1 4 7 16 COREFERENCE 328 339 The solvent ENTITY 200 211 TFA (11 mL)
2 11 14 13 COREFERENCE 529 556 a white solid (861 mg, 58%) ENTITY 507 525 the title compound
3 12 20 3 COREFERENCE 507 525 the title compound ENTITY 94 123 5-Bromo-7-chloroindolin-2-one 
new rels
R13	COREFERENCE Arg1:T14 Arg2:T3
0012.ann
id ent1 ent2 type range text type2 range2 text2
0 1 17 16 COREFERENCE 601 639 a light yellow oil (105 mg, 74% yield) ENTITY 579 597 the title compound
1 2 18 2 COREFERENCE 579 597 the title compound ENTITY 17 70 8-Bromo-2-(tert-butyl)-7-methylimidazo[1,2-a]pyridine
2 3 19 1 COREFERENCE 17 70 8-Bromo-2-(tert-butyl)-7-methylimidazo[1,2-a]pyridine ENTITY 0 15 Intermediate 41
3 4 20 21 COREFERENCE 279 287 The vial ENTITY 74 90 a microwave vial 
new rels
R18	COREFERENCE Arg1:T18 Arg2:T1
R19	COREFERENCE Arg1:T17 Arg2:T1
R20	COREFERENCE Arg1:T17 Arg2:T2
0013.ann
id ent1 ent2 type range text type2 range2 text2
0 1 3 2 COREFERENCE 331 334 76e ENTITY 179 330;335 355 (E)-methyl 3-(4-((1R,3R/1S,3S)-6-bromo-2-(2-fluoro-2-methylpropyl)-3-methyl-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridin-1-yl)-3,5-difluorophenyl)acrylate (200 mg, 0.373 mmol)
1 2 5 4 COREFERENCE 425 428 17a ENTITY 357 424;429 449 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (166 mg, 0.746 mmol)
2 14 23 1 COREFERENCE 1167 1186;971 1162 (110 mg, yield 53%) the title compound (E)-methyl 3-(4-((1R,3R/1S,3S)-6-(1-ethyl-1H-pyrazol-4-yl)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridin-1-yl)-3,5-difluoroph enyl)acrylate ENTITY 7 178 (E)-methyl3-(4-((1R,3R/1S,3S)-6-(1-ethyl-1H-pyrazol-4-yl)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridin-1-yl)-3,5-difluoroph enyl)acrylate
3 15 16 15 COREFERENCE 1163 1166 76f ENTITY 1167 1186;971 1162 (110 mg, yield 53%) the title compound (E)-methyl 3-(4-((1R,3R/1S,3S)-6-(1-ethyl-1H-pyrazol-4-yl)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridin-1-yl)-3,5-difluoroph enyl)acrylate
4 16 17 15 COREFERENCE 1190 1202 a yellow oil ENTITY 1167 1186;971 1162 (110 mg, yield 53%) the title compound (E)-methyl 3-(4-((1R,3R/1S,3S)-6-(1-ethyl-1H-pyrazol-4-yl)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridin-1-yl)-3,5-difluoroph enyl)acrylate 
new rels
R17	COREFERENCE Arg1:T16 Arg2:T1
R18	COREFERENCE Arg1:T17 Arg2:T1
0014.ann
id ent1 ent2 type range text type2 range2 text2
0 5 11 1 COREFERENCE 242 273 compound 50-e (1.6g, yield 64%) ENTITY 13 26 compound 50-e
1 6 7 6 COREFERENCE 275 286 The product ENTITY 242 273 compound 50-e (1.6g, yield 64%) 
new rels
R7	COREFERENCE Arg1:T7 Arg2:T1
0016.ann
id ent1 ent2 type range text type2 range2 text2
0 11 13 12 COREFERENCE 570 582 a yellow oil ENTITY 502 566 methyl 2-(2,3-dihydrobenzofuran-5-yl)acetate (4.0 g, yield: 93%)
1 12 20 1 COREFERENCE 502 566 methyl 2-(2,3-dihydrobenzofuran-5-yl)acetate (4.0 g, yield: 93%) ENTITY 5 53 2-(7-bromo-2,3-dihydrobenzofuran-5-yl)ethan-1-ol 
new rels
R13	COREFERENCE Arg1:T13 Arg2:T1
0020.ann
id ent1 ent2 type range text type2 range2 text2
0 11 14 13 COREFERENCE 699 712 colorless oil ENTITY 679 695 (0.150 g, 94.9%)
1 12 19 12 COREFERENCE 679 695 (0.150 g, 94.9%) ENTITY 622 640 The title compound
2 13 20 1 COREFERENCE 622 640 The title compound ENTITY 22 80 N-(2-fluoro-4-(hydrazinecarbonyl)benzyl)-N-phenylacetamide 
new rels
R14	COREFERENCE Arg1:T19 Arg2:T1
R15	COREFERENCE Arg1:T14 Arg2:T1
R16	COREFERENCE Arg1:T14 Arg2:T12
0021.ann
id ent1 ent2 type range text type2 range2 text2
0 10 13 11 COREFERENCE 784 815 the title compound (33 mg, 53%) ENTITY 682 693 The product
1 11 18 1 COREFERENCE 682 693 The product ENTITY 10 201 1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-[N-((R)-α-{N-[1-(R)-2-(R)-1-(t-butoxycarbonyl)-1-hydroxy-prop-2-yl]carbamoyl}benzyl)carbamoylmethoxy]-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine 
new rels
R12	COREFERENCE Arg1:T13 Arg2:T1
0023.ann
id ent1 ent2 type range text type2 range2 text2
0 14 17 15 COREFERENCE 834 847 a brown solid ENTITY 736 830 1.1 g (48%) of 6-[(3-chloro-4-fluorophenyl)carbonyl]-1-oxa-6-azaspiro[2.5]octane-2-carbonitril
1 15 23 1 COREFERENCE 736 830 1.1 g (48%) of 6-[(3-chloro-4-fluorophenyl)carbonyl]-1-oxa-6-azaspiro[2.5]octane-2-carbonitril ENTITY 8 87 6-[(3-chloro-4-fluorophenyl)carbonyl]-1-oxa-6-azaspiro[2.5]octane-2-carbonitril 
new rels
R16	COREFERENCE Arg1:T17 Arg2:T1
0024.ann
id ent1 ent2 type range text type2 range2 text2
0 1 4 3 COREFERENCE 279 281 6a ENTITY 239 278;282 301;374 375 1-(benzo[b]thiophen-2-yl)propan-2-amine (155 mg, 0.811 mmol )
1 2 6 5 COREFERENCE 430 432 1b ENTITY 380 429;433 452 2-fluoro-2-methylpropyl trifluoromethanesulfonate (545 mg, 2.43 mmol)
2 10 14 12 COREFERENCE 882 894 a yellow oil ENTITY 765 856;860 878 the title compound N-(1-(benzo[b]thiophen-2-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine (75 mg, yield 35%)
3 11 13 12 COREFERENCE 857 859 6b ENTITY 765 856;860 878 the title compound N-(1-(benzo[b]thiophen-2-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine (75 mg, yield 35%)
4 12 18 2 COREFERENCE 765 856;860 878 the title compound N-(1-(benzo[b]thiophen-2-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine (75 mg, yield 35%) ENTITY 166 238 N-(1-(benzo[b]thiophen-2-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine 
new rels
R13	COREFERENCE Arg1:T13 Arg2:T2
R14	COREFERENCE Arg1:T14 Arg2:T2
0025.ann
id ent1 ent2 type range text type2 range2 text2
0 12 14 13 COREFERENCE 993 1008 a colorless gum ENTITY 805 989 N,N'-(((((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis(methylene))bis(oxy))bis(2-methoxypyridine-6,3-diyl))bis(methylene))bis(azanediyl))bis(ethane-2,1-diyl))diacetamide (230 mg, 33%)
1 13 15 1 COREFERENCE 805 989 N,N'-(((((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis(methylene))bis(oxy))bis(2-methoxypyridine-6,3-diyl))bis(methylene))bis(azanediyl))bis(ethane-2,1-diyl))diacetamide (230 mg, 33%) ENTITY 7 177 N,N'-(((((((2,2'-Dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis(methylene))bis(oxy))bis(2-methoxypyridine-6,3-diyl))bis(methylene))bis(azanediyl))bis(ethane-2,1-diyl))diacetamide 
new rels
R14	COREFERENCE Arg1:T14 Arg2:T1
0028.ann
id ent1 ent2 type range text type2 range2 text2
0 6 8 7 COREFERENCE 492 507 a white crystal ENTITY 422 488 (R)-3-aminoquinuclidine.monosulfate (4.85 g: 21.6 mmol, yield=78%)
1 7 12 1 COREFERENCE 422 488 (R)-3-aminoquinuclidine.monosulfate (4.85 g: 21.6 mmol, yield=78%) ENTITY 24 59 (R)-3-aminoquinuclidine.monosulfate 
new rels
R8	COREFERENCE Arg1:T8 Arg2:T1
0032.ann
id ent1 ent2 type range text type2 range2 text2
0 1 10 2 COREFERENCE 200 202 3b ENTITY 149 199;203 221 3-(2-((2-fluoro-2-methylpropyl)amino)propyl)phenol (113 mg, 0.5 mmol)
1 2 15 5 COREFERENCE 314 316 1e ENTITY 262 313;317 335 (E)-methyl 3-(3,5-difluoro-4-formylphenyl) acrylate (113 mg, 0.5 mmol)
2 9 19 14 COREFERENCE 570 712;716 733 (E)-methyl 3-(3,5-difluoro-4-((1S,3R/1R,3S)-2-(2-fluoro-2-methylpropyl)-6-hydroxy-3-methyl-1,2, 3,4-tetrahydroisoquinolin-1-yl)phenyl)acrylate (15 mg, yield 7%) ENTITY 551 569 the title compound
3 10 20 11 COREFERENCE 713 715 3c ENTITY 570 712;716 733 (E)-methyl 3-(3,5-difluoro-4-((1S,3R/1R,3S)-2-(2-fluoro-2-methylpropyl)-6-hydroxy-3-methyl-1,2, 3,4-tetrahydroisoquinolin-1-yl)phenyl)acrylate (15 mg, yield 7%)
4 11 21 12 COREFERENCE 737 751 a yellow solid ENTITY 713 715 3c
5 12 13 1 COREFERENCE 551 569 the title compound ENTITY 7 148 (E)-methyl 3-(3,5-difluoro-4-((1S,3R/1R,3S)-2-(2-fluoro-2-methylpropyl)-6-hydroxy-3-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenyl)acrylate 
new rels
R13	COREFERENCE Arg1:T19 Arg2:T1
R14	COREFERENCE Arg1:T20 Arg2:T14
R15	COREFERENCE Arg1:T20 Arg2:T1
R16	COREFERENCE Arg1:T21 Arg2:T14
R17	COREFERENCE Arg1:T21 Arg2:T11
R18	COREFERENCE Arg1:T21 Arg2:T1
0033.ann
id ent1 ent2 type range text type2 range2 text2
0 1 9 1 COREFERENCE 257 268 COMPOUND 14 ENTITY 18 255 (S)-3-(3,5-DIFLUOROPHENYL)-N-((2R,6S,8AS,14AS,20S,23AS)-2,6-DIMETHYL-5,8,14,19,23-PENTAOXOOCTADECAHYDRO-1H,5H,14H,19H-PYRIDO[2,1-I]DIPYRROLO[2,1-C:2',1'-L]OXA[4,7,10,13]TETRAAZACYCLOHEXADECIN-20-YL)-2-(3-(4-ETHYLPHENYL)UREIDO)PROPANAMIDE
1 2 10 2 COREFERENCE 271 282 Compound 14 ENTITY 257 268 COMPOUND 14
2 6 12 3 COREFERENCE 489 500 Compound 14 ENTITY 271 282 Compound 14
3 7 8 7 COREFERENCE 517 551 a ligh yellow solid (35.7 mg, 44%) ENTITY 489 500 Compound 14 
new rels
R8	COREFERENCE Arg1:T10 Arg2:T1
R9	COREFERENCE Arg1:T12 Arg2:T1
R10	COREFERENCE Arg1:T12 Arg2:T2
R11	COREFERENCE Arg1:T8 Arg2:T1
R12	COREFERENCE Arg1:T8 Arg2:T2
R13	COREFERENCE Arg1:T8 Arg2:T3
0034.ann
id ent1 ent2 type range text type2 range2 text2
0 1 13 1 COREFERENCE 126 233 1-(Cyclopropylmethyl)-6-(2-(2,4-dimethylthiazol-5-yl)ethyl)-4-methyl-pyrazolo [4,3 - d]pyrimidine-5,7-dione ENTITY 11 118 1-(Cyclopropylmethyl)-6-(2-(2,4-dimethylthiazol-5-yl)ethyl)-4-methyl-pyrazolo [4,3 - d]pyrimidine-5,7-dione
1 11 12 2 COREFERENCE 762 896 1-(cyclopropylmethyl)-6-(2-(2,4-dimethylthiazol-5-yl)ethyl)-4-methyl-pyrazolo[4,3-d]pyrimidine-5,7-dione (20.0 mg) with a yield of 25% ENTITY 126 233 1-(Cyclopropylmethyl)-6-(2-(2,4-dimethylthiazol-5-yl)ethyl)-4-methyl-pyrazolo [4,3 - d]pyrimidine-5,7-dione 
new rels
R12	COREFERENCE Arg1:T12 Arg2:T1
0035.ann
id ent1 ent2 type range text type2 range2 text2
0 5 12 6 COREFERENCE 670 695 the compound of Example 7 ENTITY 511 641 1-(4-(dimethylamino)piperidin-1-yl)-3-hydroxy-3-(1-methyl-1H-imidazol-2-yl)propan-1-one hydrochloride (0.0220 g, 0.0623 mmol, 79%)
1 6 13 1 COREFERENCE 511 641 1-(4-(dimethylamino)piperidin-1-yl)-3-hydroxy-3-(1-methyl-1H-imidazol-2-yl)propan-1-one hydrochloride (0.0220 g, 0.0623 mmol, 79%) ENTITY 25 126 1-(4-(dimethylamino)piperidin-1-yl)-3-hydroxy-3-(1-methyl-1H-imidazol-2-yl)propan-1-one hydrochloride
2 7 8 7 COREFERENCE 700 713 a white solid ENTITY 670 695 the compound of Example 7 
new rels
R8	COREFERENCE Arg1:T12 Arg2:T1
R9	COREFERENCE Arg1:T8 Arg2:T1
R10	COREFERENCE Arg1:T8 Arg2:T6
0036.ann
id ent1 ent2 type range text type2 range2 text2
0 1 16 1 COREFERENCE 16 82 5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-methoxypyridine ENTITY 0 15 Intermediate 6B
1 14 15 2 COREFERENCE 631 736 the title compound 5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-methoxypyridine (2.71 g, 95% yield) ENTITY 16 82 5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-methoxypyridine 
new rels
R15	COREFERENCE Arg1:T15 Arg2:T1
0038.ann
id ent1 ent2 type range text type2 range2 text2
0 15 23 1 COREFERENCE 629 660 Compound 132 (64 mg, 66% yield) ENTITY 20 32 Compound 132
1 16 17 16 COREFERENCE 664 686 a yellow oily material ENTITY 629 660 Compound 132 (64 mg, 66% yield) 
new rels
R17	COREFERENCE Arg1:T17 Arg2:T1
0042.ann
id ent1 ent2 type range text type2 range2 text2
0 14 18 17 COREFERENCE 1058 1074 a colourless gum ENTITY 916 1054 (1S,3R)-1-(5-bromo-3-fluoropyridin-2-yl)-2-((1-fluorocyclopropyl)methyl)-3,5-dimethyl-1,2,3,4-tetrahydroisoquinolin-6-amine (0.672 g, 63%)
1 15 23 1 COREFERENCE 916 1054 (1S,3R)-1-(5-bromo-3-fluoropyridin-2-yl)-2-((1-fluorocyclopropyl)methyl)-3,5-dimethyl-1,2,3,4-tetrahydroisoquinolin-6-amine (0.672 g, 63%) ENTITY 15 138 (1S,3R)-1-(5-bromo-3-fluoropyridin-2-yl)-2-((1-fluorocyclopropyl)methyl)-3,5-dimethyl-1,2,3,4-tetrahydroisoquinolin-6-amine 
new rels
R16	COREFERENCE Arg1:T18 Arg2:T1
0043.ann
id ent1 ent2 type range text type2 range2 text2
0 6 15 8 COREFERENCE 760 786 the compound of Example 14 ENTITY 609 732 (S)-1-(3-(dimethylamino)piperidin-1-yl)-3-(1-methyl-1H-imidazol-2-yl)propan-1-one hydrochloride (0.0576 g, 0.171 mmol, 53%)
1 7 10 9 COREFERENCE 791 804 a white solid ENTITY 760 786 the compound of Example 14
2 8 16 2 COREFERENCE 609 732 (S)-1-(3-(dimethylamino)piperidin-1-yl)-3-(1-methyl-1H-imidazol-2-yl)propan-1-one hydrochloride (0.0576 g, 0.171 mmol, 53%) ENTITY 24 119 (S)-1-(3-(dimethylamino)piperidin-1-yl)-3-(1-methyl-1H-imidazol-2-yl)propan-1-one Hydrochloride 
new rels
R9	COREFERENCE Arg1:T15 Arg2:T2
R10	COREFERENCE Arg1:T10 Arg2:T2
R11	COREFERENCE Arg1:T10 Arg2:T8
0044.ann
id ent1 ent2 type range text type2 range2 text2
0 1 20 1 COREFERENCE 41 135 1-ethyl-N-phenyl-N-(4-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)benzyl)azetidine-3-carboxamide ENTITY 25 39 compound 11139
1 2 21 2 COREFERENCE 158 172 compound 11139 ENTITY 41 135 1-ethyl-N-phenyl-N-(4-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)benzyl)azetidine-3-carboxamide
2 17 19 18 COREFERENCE 1009 1022 a white solid ENTITY 970 1005 the title compound (0.042 g, 42.8%)
3 18 27 3 COREFERENCE 970 1005 the title compound (0.042 g, 42.8%) ENTITY 158 172 compound 11139 
new rels
R19	COREFERENCE Arg1:T19 Arg2:T3
R20	COREFERENCE Arg1:T19 Arg2:T1
R21	COREFERENCE Arg1:T19 Arg2:T2
R22	COREFERENCE Arg1:T21 Arg2:T1
R23	COREFERENCE Arg1:T27 Arg2:T1
R24	COREFERENCE Arg1:T27 Arg2:T2
0045.ann
id ent1 ent2 type range text type2 range2 text2
0 12 14 13 COREFERENCE 948 967 a light brown solid ENTITY 818 944 (6S,8R)-6-(5-bromopyridin-2-yl)-7-(2,2-difluoroethyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinoline (438 mg, 60%)
1 13 21 1 COREFERENCE 818 944 (6S,8R)-6-(5-bromopyridin-2-yl)-7-(2,2-difluoroethyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinoline (438 mg, 60%) ENTITY 15 127 (6S,8R)-6-(5-bromopyridin-2-yl)-7-(2,2-difluoroethyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinoline 
new rels
R14	COREFERENCE Arg1:T14 Arg2:T1
0046.ann
id ent1 ent2 type range text type2 range2 text2
0 5 7 6 COREFERENCE 521 536 a white crystal ENTITY 449 517 racemic 3-aminoquinuclidine.diacetate (4.41 g: 39.0 mmol, yield=89%)
1 6 11 1 COREFERENCE 449 517 racemic 3-aminoquinuclidine.diacetate (4.41 g: 39.0 mmol, yield=89%) ENTITY 36 73 racemic 3-aminoquinuclidine.diacetate 
new rels
R7	COREFERENCE Arg1:T7 Arg2:T1
0049.ann
id ent1 ent2 type range text type2 range2 text2
0 1 11 1 COREFERENCE 112 205 7-(Cyclopropylmethyl)-1-(5-isopropylisoxazol-4-yl)methyl)-3-methyl-1H-purine-2,6(3H,7H)-dione ENTITY 11 104 7-(Cyclopropylmethyl)-1-(5-isopropylisoxazol-4-yl)methyl)-3-methyl-1H-purine-2,6(3H,7H)-dione
1 9 10 2 COREFERENCE 638 761 7-(cyclopropylmethyl)-1-(5-isopropylisoxazol-4-yl)methyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (80.0 mg) with a yield of 37% ENTITY 112 205 7-(Cyclopropylmethyl)-1-(5-isopropylisoxazol-4-yl)methyl)-3-methyl-1H-purine-2,6(3H,7H)-dione 
new rels
R10	COREFERENCE Arg1:T10 Arg2:T1