Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1]Br.[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([CH2:14][N:15]([CH3:31])[C:16]([C:18]1[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[O:20][C:19]=1[CH2:27][CH2:28][CH2:29][CH3:30])=[O:17])[CH:8]=[CH:7]2>C(O)(=O)C>[Br:1][C:5]1[C:4]([OH:3])=[CH:13][CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9]([CH2:14][N:15]([CH3:31])[C:16]([C:18]1[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[O:20][C:19]=1[CH2:27][CH2:28][CH2:29][CH3:30])=[O:17])=[CH:10]2
Reactant: BrBr
Reactant: CCCCc1oc2ccccc2c1C(=O)N(C)Cc1ccc2cc(O)ccc2c1
Solvent: CC(=O)O
Product: CCCCc1oc2ccccc2c1C(=O)N(C)Cc1ccc2c(Br)c(O)ccc2c1
Reaction time: 8 h
Yield: 100 %

Procedure:
A solution of bromine in 40 mL glacial acetic acid was added dropwise under nitrogen over 2.5 h to a solution of 2-butyl-benzofuran-3-carboxylic acid (6-hydroxy-naphthalen-2-ylmethyl)-methyl-amide (0.5364 g, 1.358 mmol), prepared in the previous step, in 60 mL of glacial acetic acid. The reaction stirred for 20 h (overnight). The solvent was removed under reduced pressure. The residue was diluted with methylene chloride, extracted with 5% NaHCO3, dried (MgSO4) and the solvent removed under reduced pressure to give 2-butyl-benzofuran-3-carboxylic acid (5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-methyl-amide (0.6981 g, 100%.) as a light yellow foam, MS m/z: 466 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([O:8][C@H:9]2[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:4]([CH3:14])[C:3]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][O:22][C:23]2[CH:36]=[CH:35][C:26]3[C@H:27]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[CH2:28][O:29][C:25]=3[CH:24]=2)[CH:16]=1.[C:37](OC(=O)C)(=[O:39])[CH3:38].C(N(CC)CC)C>ClCCl>[C:37]([N:11]1[CH2:12][CH2:13][C@H:9]([O:8][C:6]2[CH:7]=[C:2]([CH3:1])[C:3]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][O:22][C:23]4[CH:36]=[CH:35][C:26]5[C@H:27]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[CH2:28][O:29][C:25]=5[CH:24]=4)[CH:16]=3)=[C:4]([CH3:14])[CH:5]=2)[CH2:10]1)(=[O:39])[CH3:38]
Reactant: CC(=O)OC(C)=O
Reactant: COC(=O)C[C@@H]1COc2cc(OCc3cccc(-c4c(C)cc(O[C@H]5CCNC5)cc4C)c3)ccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C[C@@H]1COc2cc(OCc3cccc(-c4c(C)cc(O[C@H]5CCN(C(C)=O)C5)cc4C)c3)ccc21
Reaction time: 2 h
Yield: 94.4 %

Procedure:
The crude methyl 2-((S)-6-((2′,6′-dimethyl-4′-((S)-pyrrolidin-3-yloxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 8a (45 mg, 0.09 mmol) were dissolved in 3 mL of dichloromethane, followed by addition of acetic anhydride (13 mg, 0.11 mmol) and triethylamine (18 mg, 0.18 mmol). The reaction solution was stirred for 2 hours. The resulting solution was mixed with 20 mL of dichloromethane. The organic phase was washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain the crude title compound methyl 2-((S)-6-((4′-(((S)-1-acetylpyrrolidin-3-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 9a (45 mg, yield 92.5%) as a colorless oil.
Reaction SMILES: [CH2:1]([N:5]=[C:6]=[S:7])[CH:2]([CH3:4])[CH3:3].[Cl:8][C:9]1[CH:28]=[CH:27][C:12]2[O:13][C:14]3[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=3[C@@H:16]3[C@H:21]([NH2:22])[CH2:20][CH2:19][CH2:18][N:17]3[C:11]=2[CH:10]=1>C1COCC1>[Cl:8][C:9]1[CH:28]=[CH:27][C:12]2[O:13][C:14]3[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=3[C@@H:16]3[C@H:21]([NH:22][C:6]([NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[S:7])[CH2:20][CH2:19][CH2:18][N:17]3[C:11]=2[CH:10]=1
Reactant: CC(C)CN=C=S
Reactant: N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12
Solvent: C1CCOC1
Product: CC(C)CNC(=S)N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12
Temperature: 25 °C
Reaction time: 18 h
Yield: 12 %

Procedure:
Isobutyl isothiocyanate (3.35 mg, 0.03 mmol) was added to trans-7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (5 mg, 0.02 mmol) in 1 mL of THF. The resulting mixture was stirred at room temperature for 18 h. The mixture was evaporated under reduced pressure. Crystallisation from methanol gave trans-N-(7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-N′-(2-methylpropyl)thiourea (1 mg, 12%). Data: (m/z)=416 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][N:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[C:8](I)[C:7]1=[O:22].[Li+].[Cl-].[CH3:28][Sn](C)(C)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][N:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[C:8]([CH3:28])[C:7]1=[O:22]
Reactant: O=c1c(I)c(OCc2ccc(F)cc2)ccn1Cc1cccc(F)c1
Reactant: C[Sn](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: Cc1c(OCc2ccc(F)cc2)ccn(Cc2cccc(F)c2)c1=O

Procedure:
To a degassed solution of 1-(3-fluorobenzyl)-4-[(4-fluorobenzyl)oxy]-3 iodopyridin-2(1H)-one (0.804 g, 1.7 mmol) in DMF (10 mL) and LiCl (0.25 g, 5.9 mmol) was added tetramethyltin (0.49 mL, 3.54 mmol) followed by bistriphenylphosphine-palladium chloride catalyst (0.124 g, 0.177 mmol). The reaction mixture was heated in an oil bath (85°-90° C.) under nitrogen for 3 hours. The solvent was concentrated and the residue was diluted with ethyl acetate and washed with water. The organic extracts were dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified by flash column chromatography (20% ethyl acetate in hexane). The appropriate fractions were concentrated. 1H-NMR (CD3OD, 400 MHz) δ 7.59 (d, 1H, J=7.6 Hz), 7.46 (m, 2H), 7.34 (m, 1H), 7.10 (m, 4H), 6.46 (d, 1H, J=7.6 Hz), 5.17 (s, 2H), 5.15 (s, 2H), 1.99 (s, 3H); ES-HRMS m/z 342.1314 (M+H calculated for C20H18NO2F2 requires 342.1300).
Reaction SMILES: CC([O:4][C@:5]1([C:24]#[CH:25])[C@@:9]2([CH3:23])[CH2:10][CH2:11][C@@H:12]3[C@@H:22]4[C:16](=[CH:17][C:18]([CH2:20][CH2:21]4)=[O:19])[CH2:15][CH2:14][C@H:13]3[C@@H:8]2[CH2:7][CH2:6]1)=O.C[C@@]12[C@](O)(C#C)CC[C@H]1[C@@H]1CCC3CC(=O)CCC=3[C@H]1CC2.CC(O[C@@H]1C=C2[C@@H]([C@@H]3[C@@H](CC2)[C@@H]2CC[C@@](OC(C)=O)(C#C)[C@@]2(C)CC3)CC1)=O.CC[C@@]12C(O)(C#C)CC[C@H]1[C@@H]1CCC3[C@@H]([C@H]1CC2)CCC(=O)C=3>>[CH3:23][C@@:9]12[C@:5]([OH:4])([C:24]#[CH:25])[CH2:6][CH2:7][C@H:8]1[C@@H:13]1[CH2:14][CH2:15][C:16]3[C@@H:22]([C@H:12]1[CH2:11][CH2:10]2)[CH2:21][CH2:20][C:18](=[O:19])[CH:17]=3
Reactant: C#C[C@]1(OC(C)=O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@@]21C
Agent: C#CC1(O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@@]21CC
Agent: C#C[C@]1(O)CC[C@H]2[C@@H]3CCC4=C(CCC(=O)C4)[C@H]3CC[C@@]21C
Agent: C#C[C@]1(OC(C)=O)CC[C@H]2[C@@H]3CCC4=C[C@@H](OC(C)=O)CC[C@@H]4[C@H]3CC[C@@]21C
Product: C#C[C@]1(O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@@]21C

Procedure:
17-Hydroxy-19-nor-17a-pregna-4-en-20-yn-3-one. ##STR3## Norethindrone acetate [C20H28O3 ]. 17-oxyacetate-19-nor-17a-pregn-4-en-20-yn-3-one. ##STR4## Norethynodrel [C20H26O2 ]. 17-Hydroxy-19-nor-17a-pregn-5(10)-en-20-yn-3-one. ##STR5## Ethynodiol diacetate [C24H32O4 ]. 19-Nor-17a-pregn-4-en-20-yne-3B-17-diacetate. ##STR6## Norgestrel [C21H28O2 ]. 13-Ethyl-17-hydroxy-18, 19-dinor-17a-pregn-4-en-20-yn-3-one. ##STR7##
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH3:13])=[CH:8][C:7]=1[C:15]([O:17]C)=[O:16]>[OH-].[K+]>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH3:13])=[CH:8][C:7]=1[C:15]([OH:17])=[O:16]
Reactant: COC(=O)c1cc(C(C)=O)ccc1-c1ccco1
Agent: [K+]
Agent: [OH-]
Product: CC(=O)c1ccc(-c2ccco2)c(C(=O)O)c1

Procedure:
4-(2-furyl)-3-(methoxycarbonyl)phenyl-1-ethanone (3.85 g, 15.78 mmol) was heated to reflux in 20% methanolic potassium hydroxide (200 ml) for 15 minutes. Most of the methanol was removed under reduced pressure. The residue was dissolved in water and washed with methylene chloride. The aqueous solution was acidified to pH 1 with 12N hydrochloric acid and the product extracted with ethyl acetate. The organic solution was washed with water and brine, dried over sodium sulfate, filtered, and evaporated. The crude product was recrystallized from toluene to give the title compound.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH:8]([OH:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.[Br:11][C:12]1[CH:13]=[C:14]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[NH2:15].C(O)(=O)C>O1CCOCC1.ClCCl>[Br:11][C:12]1[CH:13]=[C:14]([NH:15][C:2]2[N:7]=[C:6]([CH:8]([OH:10])[CH3:9])[CH:5]=[CH:4][N:3]=2)[CH:16]=[C:17]([CH3:19])[CH:18]=1
Reactant: Cc1cc(N)cc(Br)c1
Reactant: CC(O)c1ccnc(Cl)n1
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: C1COCCO1
Product: Cc1cc(Br)cc(Nc2nccc(C(C)O)n2)c1
Temperature: 25 °C

Procedure:
1-(2-Chloropyrimidin-4-yl)ethanol (5.25 g, 33.1 mmol) and 3-bromo-5-methylaniline (9.24 g, 49.7 mmol) were suspended in 1,4-dioxane (30 mL). Acetic acid (1.90 ml, 33.1 mmol) was added, and the resultant mixture was heated to 100° C. for 14 h. The reaction mixture was allowed to cool to room temperature and then was diluted with dichloromethane. The resultant solution was adsorbed on silica gel and purified by column chromatography on silica (10-100% ethyl acetate/hexanes) to afford 1-(2-((3-bromo-5-methylphenyl)amino)pyrimidin-4-yl)ethanol as a black semi-solid. MS ESI calc'd. for C13H15BrN3O [M+H]+ 308, 310. found 308, 310.
Reaction SMILES: C(O[CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH2:17])[C:15](=[O:18])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.[N-:19]=[N+:20]=[N-:21].[Na+].C(=O)(O)[O-].[Na+].Cl>P([O-])([O-])([O-])=O>[NH2:17][CH:16]1[C:15](=[O:18])[N:10]2[C:11]([C:12]([OH:14])=[O:13])=[C:6]([CH2:5][N:19]=[N+:20]=[N-:21])[CH2:7][S:8][C@H:9]12
Reactant: [N-]=[N+]=[N-]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Agent: Cl
Agent: O=C([O-])O
Agent: O=P([O-])([O-])[O-]
Product: [N-]=[N+]=NCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Yield: 40 %

Procedure:
To a stirred suspension of 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylic acid (45.3 g.) in a phosphate buffer (pH 6.4; 700 ml.) was added sodium azide (10.8 g.), then in small portions sodium bicarbonate (14 g.). The stirred mixture was then immersed in a 60° bath for 6 hours, the pH being maintained at 6.4 by addition of 2N aqueous HCl or 5% w/v aqueous sodium bicarbonate solutions. After cooling the pH of the mixture was adjusted to 3-3.5 with 2N aqueous HCl. The resulting precipitate was separated, washed with water and acetone then dried over P2O5 to give 7-amino-3-azidomethylceph-3-em-4-carboxylic acid (40%).
Reaction SMILES: [CH2:1]([C:3]1[C:4]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[C:5]([CH:9]=[O:10])[NH:6][C:7]=1I)[CH3:2].FC1C=CC(B(O)O)=CC=1.[C:31]([NH:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)(=[O:33])[CH3:32]>>[C:31]([NH:34][C:35]1[CH:40]=[C:39]([C:7]2[NH:6][C:5]([CH:9]=[O:10])=[C:4]([C:11]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])[C:3]=2[CH2:1][CH3:2])[CH:38]=[CH:37][CH:36]=1)(=[O:33])[CH3:32]
Reactant: CC(=O)Nc1cccc(B(O)O)c1
Reactant: CCc1c(I)[nH]c(C=O)c1C(=O)OCc1ccccc1
Agent: OB(O)c1ccc(F)cc1
Product: CCc1c(-c2cccc(NC(C)=O)c2)[nH]c(C=O)c1C(=O)OCc1ccccc1

Procedure:
Following the procedures described in Example 5, replacing methyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylate with benzyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylate and 4-fluorophenylboronic acid with 3-(acetylamino) phenylboronic acid, the title compound was obtained. Proton NMR for the product was consistent with the title compound. HRMS (ES) exact mass calculated for C23H23N2O4 (M+H): 391.1653. Found 391.1651
Reaction SMILES: C([O:3][C:4](=[O:18])[CH:5]=[CH:6][C:7]([CH3:17])=[CH:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[Cl:16])C.[OH-].[Na+]>CCO>[Cl:16][C:10]1[CH:11]=[C:12]([Cl:15])[CH:13]=[CH:14][C:9]=1[CH:8]=[C:7]([CH3:17])[CH:6]=[CH:5][C:4]([OH:18])=[O:3]
Reactant: CCOC(=O)C=CC(C)=Cc1ccc(Cl)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C=CC(=O)O)=Cc1ccc(Cl)cc1Cl
Temperature: 50 °C
Yield: 9.4 %

Procedure:
5-(2,4-Dichlorophenyl)-4-methylpenta-2,4-dienoic acid ethyl ester (2.37 g, 0.083 mol) was suspended in EtOH (50 mL). 2 N NaOH (13 mL, 3 eq) was added and the mixture was heated at 50° C. for 1 hour. The mixture was cooled to room temperature and acidified to pH 1. The resulting solid was collected to give 2 g of 5-(2,4-dichlorophenyl)-4-methylpenta-2,4-dienoic acid.
Reaction SMILES: C(=O)=O.[CH3:4][C:5]([CH3:7])=O.[CH:8]1[C:20]2[NH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]=[CH:10][CH:9]=1.[NH2-].[Na+].N.BrCC#C>>[CH:5]1[C:7]2[N:19]([CH2:20][C:8]#[CH:9])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]=[CH:10][CH:4]=1
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Reactant: CC(C)=O
Agent: C#CCBr
Agent: N
Agent: O=C=O
Product: C#CCn1c2ccccc2c2ccccc21
Temperature: -33 °C
Reaction time: 2.5 h

Procedure:
A 3,000 ml, 3-necked, round bottom flask was fitted with mechanical stirrer, addition funnel, Dry Ice/acetone reflux condenser and means for providing nitrogen atmosphere. To the flask was added 75 g (0.45 mole) of carbazole, 20 g (0.50 mole) of sodium amide, and 1500 ml of liquid ammonia. After stirring vigorously at -33° C. for about 2.5 hr, 75 g (0.63 mole) of 3-bromo-1-propyne was added dropwise over a period of 1 hr to the reaction mixture at -55° C. After the addition, stirring was continued for an additional 5 hrs, and the ammonia was allowed to evaporate overnight. The residue in the reaction flask was extracted with hexane four times. In each extraction, 3,000 ml of hexane was used and the hexane mixture was stirred vigorously with a mechanical stirrer for about 5 hrs at room temperature. Removal of the solvent from each fraction gave the desired product: fraction #1=24 g (m.p. 94°-100° C.); fraction #2=21 g (m.p. 103°-106° C.); fraction #3=25 g (m.p. 104°-106° C.); and fraction #4=17 g (m.p. 100°-106° C.). The combined crystals (87 g, 94% yield) were recrystallized from hexane at a concentration of 7 g per 100 ml of hexane, giving 60 g of plate-like crystals, m.p. 104°-107° C. IR (KBr pellet) in cm-1 : 3250 (C≡CH), 2120 (C≡C), 1620+1590 (C=C), 1480 (CH2), 1450+1320 (C--N), 740+720 (Ar), 680+660 (C≡CH). Anal: calculated for C15H11N: C, 87.77%; H, 5.40%; N, 6.82%; found: C, 88.01%; H, 5.54%; N, 6.57%.
Reaction SMILES: [F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@H:20]([CH:28]=[O:29])[CH2:19][CH2:18][O:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:32]([Mg]Br)[CH:33]=[CH2:34].ClB([C@@H]1C[C@@H]2C[C@@H](C2(C)C)[C@H]1C)[C@@H]1C[C@@H]2C[C@@H](C2(C)C)[C@H]1C>>[CH2:34]([C@@H:28]([C@@H:20]1[CH2:19][CH2:18][O:17][C@H:16]([O:15][C@@H:13]([C:5]2[CH:4]=[C:3]([C:2]([F:30])([F:1])[F:31])[CH:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:6]=2)[CH3:14])[C@H:21]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[OH:29])[CH:33]=[CH2:32]
Reactant: C=CC[Mg]Br
Reactant: C[C@@H](O[C@H]1OCC[C@@H](C=O)[C@@H]1c1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: C[C@@H]1[C@H]2C[C@@H](C[C@H]1B(Cl)[C@@H]1C[C@@H]3C[C@H]([C@H]1C)C3(C)C)C2(C)C
Product: C=CC[C@H](O)[C@@H]1CCO[C@H](O[C@H](C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H]1c1ccccc1

Procedure:
Prepared from (2R,3R,4R)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-tetrahydro-3-phenyl-2H-pyran-4-carboxaldehyde (WO 00/56727A1), allylmagnesium bromide and chlorobis[(1R,2S,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]borane according to the method of Description 31.
Reaction SMILES: Cl.[NH2:2][C:3]1([C:9]([OH:11])=[O:10])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[CH3:12][Si](C=[N+]=[N-])(C)C.C(OCC)C>CO>[NH2:2][C:3]1([C:9]([O:11][CH3:12])=[O:10])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: NC1(C(=O)O)CCOCC1
Agent: Cl
Solvent: CO
Solvent: CCOCC
Product: COC(=O)C1(N)CCOCC1
Temperature: 25 °C
Reaction time: 96 h
Yield: 99 %

Procedure:
To a solution of 4-amino-4-carboxy-tetrahydropyrane hydrochloride (2 g) in methanol was added dropwise a solution of 2M trimethylsilyldiazomethane-diethylether (33 mL) under ice-cooling, and the mixture was stirred at room temperature for 4 days. The reaction mixture was concentrated in vacuo, and the resultant crude product was dissolved in hexane-diethylether (1 mL/1 mL), and thereto was added an aqueous 4N hydrochloric acid. The precipitates were collected by filtration to give 4-amino-4-methoxycarbonyl-tetrahydropyrane (2.13 g, yield: 99%) as white-crystals.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:6])[C:4]#[CH:5].Br[CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14]>C1COCC1.O>[CH3:14][O:13][CH2:12][CH2:11][O:10][CH2:9][CH2:8][O:6][CH2:3][C:4]#[CH:5]
Reactant: COCCOCCBr
Reactant: C#CCO
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: C#CCOCCOCCOC
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 3 %

Procedure:
To a stirred suspension of sodium hydride (3.12 g, 78.0 mmol) in THF (100 mL) cooled to 5° C. in an ice-bath was added a solution of propargyl alcohol (4.60 g, 78.0 mmol) in THF (20 mL) drop-wise. The mixture was stirred at 5° C. for 30 min and was then allowed to warm to RT and treated dropwise with 1-bromo-2-(2-methoxyethoxy)ethane (7.00 mL, 52.0 mmol). The reaction mixture was stirred at RT for 16 hr and was then, diluted with water (100 mL) and extracted with diethyl ether (2×100 mL). The combined organic extracts were dried, filtered and evaporated in vacuo. The residue was purified by flash column chromatography, eluting with 30% EtOAc in heptane, to afford the title compound (9) (250 mg, 9%) as a colourless oil: 1H NMR (500 MHz, MeOD) δ: 4.18 (2H, d), 3.66-3.69 (2H, m), 3.60-3.66 (4H, m), 3.52-3.56 (2H, m), 3.36 (3H, s), 2.84 (1H, t).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH2:27])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].Br[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)[N:30]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4N)cc3)cc2)CC1
Reactant: Brc1cccc(-c2ccccc2)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(-c5ccccc5)n4)cc3)cc2)CC1

Procedure:
1-[4′-(4-Amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester (0.250 g, 0.689 mmol), 2-bromo-6-phenyl-pyridine (0.1457 g, 0.62 mmol), cesium carbonate (0.2694 g, 0.826 mmol) and (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.032 g, 0.052 mmol) were dissolved in toluene (3 mL) and the solution was degassed with bubbling N2 (g).
Reaction SMILES: [C:1]1([CH3:10])[C:2]([C:7]([OH:9])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[Cl:11][S:12](O)(=[O:14])=[O:13]>>[Cl:11][S:12]([C:4]1[CH:5]=[CH:6][C:1]([CH3:10])=[C:2]([CH:3]=1)[C:7]([OH:9])=[O:8])(=[O:14])=[O:13]
Reactant: Cc1ccccc1C(=O)O
Reactant: O=S(=O)(O)Cl
Product: Cc1ccc(S(=O)(=O)Cl)cc1C(=O)O
Temperature: 100 °C
Yield: 78 %

Procedure:
A mixture of o-toluic acid (15 g, 0.11 mol) and chlorosulfonic acid (30 ml) was heated at 100° C. under nitrogen for 2.5 h. The reaction mixture was then poured onto ice (500 ml) and the resulting precipitate was filtered, yielding the title compound as an off-white solid (20 g, 78% yield). MP 151–155° C.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[O:11][CH2:12][C@@H:13]2[CH2:17][O:16]C(C)(C)[O:14]2)=[C:4]([Cl:20])[N:3]=1>C(O)(=O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[O:11][CH2:12][C@@H:13]([OH:14])[CH2:17][OH:16])=[C:4]([Cl:20])[N:3]=1
Reactant: CC1(C)OC[C@@H](COn2cnc3c(Cl)nc(N)nc32)O1
Solvent: CC(=O)O
Product: Nc1nc(Cl)c2ncn(OC[C@@H](O)CO)c2n1
Reaction time: 1 h

Procedure:
A solution of (S)-2-amino-6-chloro-9-(2,2-dimethyl-1,3-dioxolan-4-ylmethoxy)purine (250 mg, 0.83 mmol) in 80% acetic acid (20 ml) was stirred at 25° C. for 2 h. and then at 70° C. for 1 h. The solution was evaporated to dryness under reduced pressure, the residue absorbed on silica and chromatographed eluting with acetone-hexane 3:1 affording (S)-2-amino-6-chloro-9-(2,3-dihydroxyprop-1-oxy)purine (170 mg, 78%) as a white solid; m.p. 155°-8° C. υmax (KBr) 3340, 3200, 1660, 1620, 1560, 1520 1470 cm-1 ; δH[(CD3)2SO] 3.41(2H,m,CH2OH) 3.78(1H,m,CH), 4.19(1H,q,J7.4,10.4 Hz,CH2ON), 4.40(1H,q,J3.3,10.4 Hz,CH2ON), 4.73(1H,t,J5.0 Hz,D2O exchangeable, OH), 5.14(1H,d,J5.0 Hz.D2O exchangeable, OH), 7.12(2H,S,D2O exchangeable, NH2) 8.35(1H,S,H-8). Found M+ 259.0475; C8H10ClN5O3 requires M+ 259.0472.
Reaction SMILES: [Na].[CH3:2][C:3]1[CH:8]=[C:7]([OH:9])[CH:6]=[C:5]([CH3:10])[C:4]=1[N:11]=[N:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Br[CH2:20][CH2:21][CH3:22]>>[CH3:2][C:3]1[CH:8]=[C:7]([O:9][CH2:20][CH2:21][CH3:22])[CH:6]=[C:5]([CH3:10])[C:4]=1[N:11]=[N:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Cc1cc(O)cc(C)c1N=Nc1ccccc1
Reactant: CCCBr
Agent: [Na]
Product: CCCOc1cc(C)c(N=Nc2ccccc2)c(C)c1
Reaction time: 8 h
Yield: 93.1 %

Procedure:
To a solution of sodium (2.0 g) in absolute alcohol (120 ml) was added 2,6-dimethyl-4-hydroxyazobenzene (18.3 g) and 1-bromo propane (20 g). The mixture was refluxed for three hours and was left overnight at room temperature. A precipitate of sodium bromide was filtered off, was washed with some cold absolute ethanol, and was discarded. The alcohol was removed from the filtrate by distillation, the residue was dissolved in ether (200 ml), and was extracted with 2% sodium hydroxide solution (4×50 ml) and once with water. After drying (Na2SO4) and filtering, the ether solution was evaporated to dryness leaving a residual oily material (20.2 g), sufficiently pure for the following reaction step.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.Cl[CH2:17][CH:18]([OH:27])[CH2:19][CH2:20][C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1.[OH-].[Na+]>C(O)C.O>[C:10]1(/[CH:9]=[CH:8]/[C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:17][CH:18]([OH:27])[CH2:19][CH2:20][C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)=[CH:7][CH:6]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: OC(CCl)CCc1cccnc1
Reactant: Oc1ccc(/C=C/c2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: OC(CCc1cccnc1)COc1ccc(/C=C/c2ccccc2)cc1
Yield: 40.2 %

Procedure:
Prepared according to the method described in Example 24b) from trans-4-hydroxystilbene (2.6 g), (±)-α-(chloromethyl)-3-pyridinepropanol (2.5 g) and sodium hydroxide (0.54 g) in ethanol (50 ml) and water (10 ml) at reflux for 2 hours to give the title compound as a solid (1.84 g)