Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([C:8]([NH:12][C:13](=[O:16])[CH2:14]Cl)([CH3:11])[CH2:9][OH:10])[CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+]>C(O)(C)(C)C>[Br:1][C:2]1[N:7]=[C:6]([C:8]2([CH3:11])[NH:12][C:13](=[O:16])[CH2:14][O:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1
Reactant: CC(CO)(NC(=O)CCl)c1cccc(Br)n1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Product: CC1(c2cccc(Br)n2)COCC(=O)N1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of N-[1-(6-bromo-pyridin-2-yl)-2-hydroxy-1-methyl-ethyl]-2-chloro-acetamide in tert-butanol (90 ml) was added KOtBu and the reaction mixture was stirred at rt for 4 h. The reaction mixture was quenched with H2O and diluted with EtOAc. The phases were separated and the aq. phase was twice extracted with EtOAc. The combined org. phases were washed with brine, dried over Na2SO4, filtered and the solvent was removed to leave the title compound as a pale yellow solid. HPLC RtH4=0.73 min; ESIMS: 271, 273 [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 8.72 (s, 1H), 7.82-7.78 (m, 1H), 7.57-7.51 (m, 2H), 4.10 (d, 2H), 4.00 (d, 1H), 3.65 (d, 1H), 1.42 (s, 3H).
Reaction SMILES: Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([Cl:11])=[CH:10][C:5]2=[N:4][CH:3]=1.C(O)(=O)C(O)=O.C([Sn](CCCC)(CCCC)[C:23]1[CH:24]=[C:25]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[CH:26]=[CH:27][CH:28]=1)CCC>CCO>[Cl:11][C:9]1[CH:8]=[CH:7][N:6]2[C:2]([C:27]3[CH:28]=[CH:23][CH:24]=[C:25]([C:29]4[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=4)[CH:26]=3)=[CH:3][N:4]=[C:5]2[CH:10]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cccc(-c2cccnc2)c1
Reactant: Clc1ccn2c(Br)cnc2c1
Agent: O=C(O)C(=O)O
Solvent: CCO
Product: Clc1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1

Procedure:
The title compound was prepared in a similar manner to that described in Example 11 from 3-bromo-7-chloroimidazo[1,2-α]pyridine and 3-[3-(tri-n-butylstannanyl)phenyl]pyridine. Oxalate salt, white crystalline solid, m.p. 178-180° C. (EtOH). 1H NMR (360 MHz, d6-DMSO) δH 7.05 (1H, dd, J 7 and 2), 7.50-7.56 (1H, m), 7.67-7.89 (4H, m), 7.96 (1H, s), 8.01 (1H, s), 8.21 (1H, d, J 7), 8.61 (1H, d, J 4), 8.70 (1H, d, J 7), 9.02 (1H, d, J 2); m/z (ES+) 306 (M++H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH:9][C:10]1[CH:11]=[C:12]([O:22][C:23]([F:26])([F:25])[F:24])[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([OH:21])=O)=[CH:15]2)(=[O:8])=[O:7].Cl.C[N:29](C)CCCN=C=NCC.CN(C)C=O>O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH:9][C:10]1[CH:11]=[C:12]([O:22][C:23]([F:25])([F:26])[F:24])[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([NH2:29])=[O:21])=[CH:15]2)(=[O:7])=[O:8]
Reactant: O=C(O)c1cc2cc(OC(F)(F)F)cc(NS(=O)(=O)c3cccs3)c2[nH]1
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Product: NC(=O)c1cc2cc(OC(F)(F)F)cc(NS(=O)(=O)c3cccs3)c2[nH]1
Temperature: 25 °C
Reaction time: 15 h
Yield: 89.4 %

Procedure:
A mixture of 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylic acid (2.50 g), 1H-1,2,3-benzotriazol-1-ol-ammonia complex (1.89 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (2.38 g) and N,N-dimethylformamide (20 mL) was stirred at room temperature for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, dried (MgSO4), and concentrated. The residue was washed with hexane to give the title compound (2.23 g, yield 89%) as pale-yellow crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point >300° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:45])[CH2:5][NH:6][C:7]([C:9]1[C:14]([O:15]CC2C=CC=CC=2)=[C:13]([CH3:23])[N:12]=[C:11]([CH2:24][CH:25]2[CH2:30][CH2:29][N:28]([C:31]3[CH:36]=[CH:35][C:34]([C:37]4[CH:42]=[CH:41][C:40]([CH2:43][OH:44])=[CH:39][CH:38]=4)=[CH:33][CH:32]=3)[CH2:27][CH2:26]2)[N:10]=1)=[O:8])[CH3:2]>C(OCC)(=O)C.ClCCl.[Pd]>[CH2:1]([O:3][C:4](=[O:45])[CH2:5][NH:6][C:7]([C:9]1[C:14]([OH:15])=[C:13]([CH3:23])[N:12]=[C:11]([CH2:24][CH:25]2[CH2:26][CH2:27][N:28]([C:31]3[CH:32]=[CH:33][C:34]([C:37]4[CH:38]=[CH:39][C:40]([CH2:43][OH:44])=[CH:41][CH:42]=4)=[CH:35][CH:36]=3)[CH2:29][CH2:30]2)[N:10]=1)=[O:8])[CH3:2]
Reactant: CCOC(=O)CNC(=O)c1nc(CC2CCN(c3ccc(-c4ccc(CO)cc4)cc3)CC2)nc(C)c1OCc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCOC(=O)CNC(=O)c1nc(CC2CCN(c3ccc(-c4ccc(CO)cc4)cc3)CC2)nc(C)c1O
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 93 %

Procedure:
Ethyl({[5-(benzyloxy)-2-({1-[4′-(hydroxymethyl)biphenyl-4-yl]piperidin-4-yl}methyl)-6-methylpyrimidin-4-yl]carbonyl}amino)acetate (0.43 g, 0.71 mmol) was dissolved in a mixed solvent of ethyl acetate (20 mL) and dichloromethane (20 mL), and 10% palladium-activated carbon (0.080 g) was added, followed by stirring at room temperature for 2.5 hours under a hydrogen atmosphere. The reaction solution was filtered with celite, and the filtrate was concentrated under reduced pressure, whereby a solid was deposited. The resulting solid was collected by filtration, and dried under reduced pressure to afford the title compound (0.34 g, 0.66 mmol) as a white solid (yield 93%).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([CH:9]([CH3:11])[CH3:10])[C:5]([NH2:6])=[C:4]([CH:12]([CH3:14])[CH3:13])[CH:3]=1.[Li]CCCC.Cl[Si:21]([CH:24]1[C:28]2[S:29][CH:30]=[CH:31][C:27]=2[C:26]([CH3:32])=[C:25]1[CH3:33])([CH3:23])[CH3:22]>C1COCC1>[Br:1][C:2]1[CH:8]=[C:7]([CH:9]([CH3:10])[CH3:11])[C:5]([NH:6][Si:21]([CH:24]2[C:28]3[S:29][CH:30]=[CH:31][C:27]=3[C:26]([CH3:32])=[C:25]2[CH3:33])([CH3:22])[CH3:23])=[C:4]([CH:12]([CH3:14])[CH3:13])[CH:3]=1
Reactant: CC1=C(C)C([Si](C)(C)Cl)c2sccc21
Reactant: CC(C)c1cc(Br)cc(C(C)C)c1N
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1=C(C)C([Si](C)(C)Nc2c(C(C)C)cc(Br)cc2C(C)C)c2sccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Under an argon atmosphere, to a solution of 18.9 g (73.8 mmol) of 4-bromo-2,6-diisopropylaniline in 200 ml of THF, 29.5 ml of 2.5 M (73.8 mmol) nBuLi in hexanes was added at −80° C. This mixture was warmed for ca. 1 hour to ambient temperature. Then, the resulting solution was added dropwise over ca. 1 hour, while vigorously stirring, to a solution of 17.9 g (73.8 mmol) of chloro(4,5-dimethyl-6H-cyclopenta[b]thien-6-yl)dimethylsilane in 100 ml of THF. The resulting mixture was stirred overnight at ambient temperature, and then, evaporated to dryness. To the residue, 150 ml of toluene was added. This mixture was filtered through a glass frit (G4). The filtrate was evaporated to dryness. Fractional distillation gave a yellow liquid, bp 180° C./0.1 mm Hg. The product crystallizes slowly at ambient temperature. Yield 11.9 g (35%).
Reaction SMILES: [CH2:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:13])[CH2:6][C:7]2=[O:12])[CH3:2].[N+:14]([O-])([OH:16])=[O:15]>CCOCC>[CH2:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:13])[CH:6]([N+:14]([O-:16])=[O:15])[C:7]2=[O:12])[CH3:2]
Reactant: CCc1cccc2c1C(=O)CC2=O
Reactant: O=[N+]([O-])O
Solvent: CCOCC
Product: CCc1cccc2c1C(=O)C([N+](=O)[O-])C2=O

Procedure:
A suspension of 4-ethyl indane-1,3-dione (0.52 g; 0.003 mole) in dry ether (5 ml) was treated dropwise at 10°C with fuming nitric acid (1.0 ml) and the precipitated product filtered after 40 mins. at room temperature; m.p. (water, hydrochloric acid) 98°-100°C; (Found; C, 59.98; H, 4.18; N, 6.34; C11H9NO4 requires: C, 60.28; H, 4.14; N, 6.39%).
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[S:18](=[O:20])(=[O:19])[CH2:17][CH2:16][C:15]([C:21]([O:23]C)=[O:22])=[CH:14][C:13]=3[CH:25]=2)=[CH:5][CH:4]=1.Cl>COCCOC>[F:26][C:2]([F:1])([F:27])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[S:18](=[O:19])(=[O:20])[CH2:17][CH2:16][C:15]([C:21]([OH:23])=[O:22])=[CH:14][C:13]=3[CH:25]=2)=[CH:7][CH:8]=1
Reactant: COC(=O)C1=Cc2cc(-c3ccc(C(F)(F)F)cc3)ccc2S(=O)(=O)CC1
Agent: Cl
Solvent: COCCOC
Product: O=C(O)C1=Cc2cc(-c3ccc(C(F)(F)F)cc3)ccc2S(=O)(=O)CC1
Temperature: 25 °C
Yield: 75.9 %

Procedure:
To a solution of methyl 7-(4-trifluoromethylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylate (600 mg) in 1,2-dimethoxyethane (40 ml) was added at room temperature 6N hydrochloric acid (20 ml), and the mixture was refluxed for 22 hours, cooled to room temperature and extracted with ethyl acetate/THF. The organic layer was washed with saturated brine, dried with magnesium sulfate and concentrated under reduced pressure to give crystals, which were collected by filtration. The crystals were washed with hexane to give colorless crystals of 7-(4-trifluoromethylphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (439.5 mg).
Reaction SMILES: C1([O:7][CH:8]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]2[S:23][CH:22]=[N:21][C:20]=2[CH3:24])[C:9]([O:11][CH3:12])=[O:10])CCCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[OH:7][CH:8]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[S:23][CH:22]=[N:21][C:20]=1[CH3:24])[C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)C(CCCCCCc1scnc1C)OC1CCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Product: COC(=O)C(O)CCCCCCc1scnc1C

Procedure:
To a solution of (E)-methyl 2-(cyclohexyloxy)-8-(4-methylthiazol-5-yl)oct-7-enoate (560 mg, 1.58 mmol) and ethanol (40 mL) was added 10% palladium on carbon (82 mg) and the resulting mixture was hydrogenated at 1 atm H2 overnight. The resulting mixture was then filtered through CELITE and concentrated in vacuo to yield methyl 2-(cyclohexyloxy)-8-(4-methylthiazol-5-yl)octanoate (97%) which was used in the next step without further purification. A solution of methyl 2-(cyclohexyloxy)-8-(4-methylthiazol-5-yl)octanoate (563 mg, 1.58 mmol), methanol (8.6 mL), and p-toluenesulfonic acid (14.8 mg, 0.086 mmol) was stirred at room temperature for 1 h. Solvent was removed in vacuo to yield methyl 2-hydroxy-8-(4-methylthiazol-5-yl)octanoate which was used in the next step without further purification. A mixture of 2-hydroxy-8-(4-methylthiazol-5-yl)octanoic acid (590 mg, 2.17 mmol), tetrahydrofuran (21 mL), water (54 mL) and lithium hydroxide (78.1 mg, 3.26 mmol) was stirred at room temperature for 2 h. The resulting mixture was acidified with 1N HCl and concentrated in vacuo. An excess amount of acetonitrile was added to the residue and the mixture was concentrated. The process was repeated twice to yield 2-hydroxy-8-(4-methylthiazol-5-yl)octanoic acid which was used in the next step without further purification. MS (ES+) 258 (M+1).
Reaction SMILES: CC1C=CC(S(OCC2CC3C=C(F)C=C(C4C=CC=CC=4Cl)C=3O2)(=O)=O)=CC=1.[N-]=[N+]=[N-].[Na+].[N:34]([CH2:37][CH:38]1[CH2:42][C:41]2[CH:43]=[C:44]([F:54])[CH:45]=[C:46]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[Cl:53])[C:40]=2[O:39]1)=[N+]=[N-].[N-]=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[Cl:53][C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=1[C:46]1[C:40]2[O:39][CH:38]([CH2:37][NH2:34])[CH2:42][C:41]=2[CH:43]=[C:44]([F:54])[CH:45]=1
Reactant: [N-]=[N+]=NCC1Cc2cc(F)cc(-c3ccccc3Cl)c2O1
Agent: Cc1ccc(S(=O)(=O)OCC2Cc3cc(F)cc(-c4ccccc4Cl)c3O2)cc1
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Product: NCC1Cc2cc(F)cc(-c3ccccc3Cl)c2O1
Yield: 70 %

Procedure:
Treatment of (±)-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (6.65 g, 0.015 mol) with sodium azide (3.99 g, 0.061 mol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran. Treatment of the azide with triphenylphosphine (4.18 g, 0.16 mol) generally according to the procedure described for Example 21 provided 3.37 g (70%) of (±)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. mp >250° C. (dec); Anal. calcd. for C15H13ClFNOHCl: C, 57.34; H, 4.49; N, 4.46. Found: C, 57.45; H, 4.75; N, 4.22.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH:23]=[CH:22][CH:21]=[C:20]1B(O)O)=[O:18])([CH3:15])([CH3:14])[CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[C:12]([O:16][C:17]([N:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
Reactant: CC(C)(C)OC(=O)n1cccc1B(O)O
Reactant: COC(=O)c1ccc(Br)nc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: COC(=O)c1ccc(-c2cccn2C(=O)OC(C)(C)C)nc1
Temperature: 100 °C
Reaction time: 15 h
Yield: 91.8 %

Procedure:
Commercially available methyl 6-bromonicotinate (650 mg, 3.01 mmol) and commercially available 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (960 mg, 4.34 mmol) were dissolved in 1,2-dimethoxyethane (30 mL), and palladium (II) acetate (34.0 mg, 0.151 mmol), triphenylphosphine (158 mg, 0.602 mol) and an aqueous potassium carbonate solution (2M, 4.5 mL, 9.00 mmol) were added, followed by stirring at 100° C. for 15 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) and ethyl acetate (30 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-20%) to afford the desired compound (835 mg, yield 92%) as a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][C:12]#[C:13][CH2:14][OH:15])=[C:4](Cl)[N:3]=1.C(O)=[O:18]>>[OH:15][CH2:14][C:13]#[C:12][CH2:11][N:8]1[CH:7]=[N:6][C:5]2[C:4](=[O:18])[NH:3][C:2]([NH2:1])=[N:10][C:9]1=2
Reactant: Nc1nc(Cl)c2ncn(CC#CCO)c2n1
Reactant: O=CO
Product: Nc1nc2c(ncn2CC#CCO)c(=O)[nH]1
Reaction time: 1 h
Yield: 70 %

Procedure:
A solution of 4-(2-amino-6-chloropurin-9-yl)-2-butyn-1-ol (140 mg, 0.59 mmol) in 2 ml of 50% aqueous formic acid was kept at 80° for 6 h and then evaporated to dryness in vacuum. The residue was dissolved in 2 ml of water--conc. aqueous ammonia 1+1 and the solution kept at 80° for 1 h and then evaporated in vacuum to dryness. Recrystallization from water afforded 90 mg (70%) of 9-(4-hydroxy-2-butynyl)guanine.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]=[C:12]=[O:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:14][C:15]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=O>>[Cl:24][C:22]1[CH:23]=[C:15]2[C:16]([C:17](=[O:19])[N:11]([S:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)(=[O:9])=[O:10])[C:12](=[O:13])[NH:14]2)=[CH:20][CH:21]=1
Reactant: Nc1cc(Cl)ccc1C(=O)O
Reactant: O=C=NS(=O)(=O)c1ccc(F)cc1
Product: O=c1[nH]c2cc(Cl)ccc2c(=O)n1S(=O)(=O)c1ccc(F)cc1
Yield: 26.8 %

Procedure:
1.72 g (8.57 mmol) of 4-fluorobenzenesulfonylisocyanate and 1.47 g (8.57 mmol) of 2-amino-4-chlorobenzoic acid were treated in the same way as in Example 1 to obtain 815 mg of the above-identified compound (yield 26.8%). Properties: colorless crystal, Melting point: >250° C., PMR (δppm, DMSO-d6): 7.12 (1H,s), 7.23 (1H,d), 7.49-7.55 (2H,m), 7.86 (1H,d), 8.23-8.28 (2H,m), 11.90 (1H,br).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:11][CH2:12][CH:13]([N:17]([CH3:28])[C:18]([O:20]CC1C=CC=CC=1)=[O:19])[C:14]([OH:16])=O.S(Cl)(Cl)=O>CCCCCC>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:11][CH2:12][CH:13]1[C:14](=[O:16])[O:20][C:18](=[O:19])[N:17]1[CH3:28]
Reactant: COc1cccc(CCC(C(=O)O)N(C)C(=O)OCc2ccccc2)c1OC
Solvent: O=S(Cl)Cl
Solvent: CCCCCC
Product: COc1cccc(CCC2C(=O)OC(=O)N2C)c1OC

Procedure:
18.5 g of 4-(2,3-dimethoxyphenyl)-2-(N-methyl-N-benzyloxycarbonyl-amino)-butyric acid (0.048 mole) and 28.7 g of thionyl chloride are placed into a 250 ml round-bottomed flask, refluxing for 2 hours then distilling off under vacuum the thionyl chloride until obtaining a thick oil. The oil is taken up into 100 ml of hexane, stirring until solidification, then it is decanted and triturated with 100 ml more of hexane, filtered and dried under vacuum at 30° C. to obtain a fine crystalline powder. Yield: 12.5 g, 93% (moles), 68% (weight).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([C:18](=O)[C:19]#[CH:20])=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH:23]1([NH:28][C:29]([NH2:31])=[NH:30])[CH2:27][CH2:26][CH2:25][CH2:24]1.[O-]CC.[Na+]>>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([C:18]3[CH:19]=[CH:20][N:31]=[C:29]([NH:28][CH:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[N:30]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: C#CC(=O)c1c(-c2cccc(Br)c2)nn2c(Cl)cccc12
Reactant: N=C(N)NC1CCCC1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Product: Clc1cccc2c(-c3ccnc(NC4CCCC4)n3)c(-c3cccc(Br)c3)nn12
Yield: 46 %

Procedure:
In a similar manner as described in Example 46 from 1-[2-(3-bromophenyl)-7-chloropyrazolo[1,5-a]pyridin-3-yl]-2-propyn-1-one (1.0 g, 2.8 mmol), N-cyclopentylguanidine hydrochloride and sodium ethoxide (4.1 mL, 21 wt % in ethanol, 3.6 mmol) at room temperature was obtained 4-[2-(3-bromophenyl)-7-chloropyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (0.60 g, 46%) as a yellow crystalline solid. MS m/z 469 (M+1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[CH2:7][CH:8]1[CH2:11][CH:10]([C:12](=[O:14])[CH3:13])[C:9]1([CH3:16])[CH3:15])([CH3:4])([CH3:3])[CH3:2].[C:18](OC)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1>C1COCC1>[C:1]([O:5][C:6](=[O:17])[CH2:7][CH:8]1[CH2:11][CH:10]([C:12](=[O:14])[CH2:13][C:18](=[O:25])[C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[C:9]1([CH3:16])[CH3:15])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1cccnc1
Reactant: CC(=O)C1CC(CC(=O)OC(C)(C)C)C1(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)CC1CC(C(=O)CC(=O)c2cccnc2)C1(C)C
Temperature: 5 °C
Reaction time: 2 h
Yield: 49.2 %

Procedure:
Tert-butyl ester 7 (47.7 g, 199 mmol) and methyl nicotinate (27.3 g, 199 mmol) were dissolved in THF (1 L) and cooled to 5° C. KOBut (44.6 g, 398 mmol) was added in 4 portions over 1 h. The reaction was stirred at 0° C. for 2 h. The reaction was quenched with saturated NH4Cl (200 mL) and concentrated to an oil. The residue was dissolved in EtOAc and washed with saturated NH4Cl (300 mL×3). The combined aqueous layers were extracted with EtOAc (100 mL×2). The organic layers were combined and dried with brine and MgSO4 and concentrated in vacuo. The residue was purified by chromatography (hexane-EtOAc, 2:1 to 1:1). Diketone 9 (33.8 g, 49%) was obtained as a yellow crystalline solid; the methyl ester of 7 (16.2 g, 26%) and a mixture (1:1) of both esters (11.5 g, 17%) were also collected as yellow crystalline solids.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[NH:6][C:5]2=O.S(Cl)([Cl:21])=O>CN(C)C=O>[Cl:21][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH3:1])[CH:3]=2)[N:8]=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:6]=1
Reactant: Cc1ccc2nc(-c3ccccc3)[nH]c(=O)c2c1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: Cc1ccc2nc(-c3ccccc3)nc(Cl)c2c1

Procedure:
To a stirred slurry of 2.1 g of 6-methyl-2-phenylquinazolin-4(3H)-one and 35 ml of thionyl chloride was added dropwise 1.3 g of dimethylformamide. The mixture was maintained at reflux temperature for 90 minutes. The mixture was concentrated under reduced pressure, the residual solid was mixed with crushed ice and the washed solid collected. Two recrystallizations from petroleum ether (60°-110° fraction) gave 1.5 g of 4-chloro-6-methyl-2-phenylquinazoline, m.p. 111°-113°.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.O.[H-].[Na+].C[O:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21](Br)[N:20]=1)=[O:18]>CC(N(C)C)=O.[Cu](I)I>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([C:17]([OH:18])=[O:16])=[N:20][C:21]=1[O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=1
Reactant: Oc1cccc(C(F)(F)F)c1
Reactant: COC(=O)c1ccc(OC)c(Br)n1
Agent: I[Cu]I
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: COc1ccc(C(=O)O)nc1Oc1cccc(C(F)(F)F)c1
Temperature: 120 °C
Reaction time: 10 h

Procedure:
3-(trifluoromethyl) phenol (1.317 g, 0.0081 mol) was dissolved in 10 ml of dried dimethyl acetamide. While cooling the obtained solution with water, sodium hydride (0.39 g (ca. 60% in mineral oil), 0.0081×1.2 mol) was added to the solution. After completion of the foaming, a solution obtained by dissolving 6-bromo-5-methoxy-2-pyridine carboxylic acid methyl ester (2.0 g, 0.0081 mol) in 10 ml of dried dimethyl acetamide, and then copper iodide (1.55 g, 0.081 mol) were successively added to the solution. The obtained mixture was heated and stirred at 120° C. for 10 hours. Thereafter, the obtained reaction solution was cooled, mixed with 50 ml of water and then with 50 ml of ethyl acetate, and filtered through a glass filter provided with Hyflo Super-Cell. The obtained filtrate was extracted with ethyl acetate to obtain an aimed product. An organic phase was separated from the product, washed with water and then dried with anhydrous sodium sulfate. The dried product was concentrated, and the obtained residues were purified by silica gel column chromatography (eluting solution: ethyl acetate/hexane).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1F.[OH:13][C:14]1[CH:19]=[CH:18][C:17]([B:20]([OH:22])[OH:21])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([B:20]([OH:22])[OH:21])=[CH:16][CH:15]=1
Reactant: OB(O)c1ccc(O)cc1
Reactant: Fc1ccc(C(F)(F)F)cc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: OB(O)c1ccc(Oc2ccc(C(F)(F)F)cc2Cl)cc1
Temperature: 130 °C
Reaction time: 20 h
Yield: 13.2 %

Procedure:
A solution of 2-chloro-1-fluoro-4-(trifluoromethyl)benzene (0.95 g), (4-hydroxyphenyl)boronic acid (0.66 g), and potassium carbonate (1.65 g) in DMSO (5.0 mL) was heated with stirring at 130° C. for 20 hours. The resultant reaction mixture was left to be cooled down and was poured into an ice water, and pH of the resultant reaction mixture was adjusted to around 2 with a 10% hydrochloric acid, followed by extracting the reaction mixture with ethyl acetate. From the organic phase, the solvent was distilled off under reduced pressure, and the resultant residue was purified by silica gel column chromatography (eluate; n-hexane:ethyl acetate 100:0 to 50:50) to obtain the subject compound (0.20 g) as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([OH:16])=O)=[CH:4][CH:3]=1.[NH:17]1[CH2:22][CH2:21][CH2:20][CH:19]([NH:23][C:24]([C:26]2[CH:27]=[CH:28][CH:29]=[C:30]3[O:34][CH:33]=[CH:32][C:31]=23)=[O:25])[CH2:18]1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:17]2[CH2:22][CH2:21][CH2:20][CH:19]([NH:23][C:24]([C:26]3[CH:27]=[CH:28][CH:29]=[C:30]4[O:34][CH:33]=[CH:32][C:31]=34)=[O:25])[CH2:18]2)=[O:16])=[CH:6][CH:7]=1
Reactant: O=C(NC1CCCNC1)c1cccc2occc12
Reactant: Cc1nc(C(=O)O)c(-c2ccc(F)cc2)s1
Product: Cc1nc(C(=O)N2CCCC(NC(=O)c3cccc4occc34)C2)c(-c2ccc(F)cc2)s1

Procedure:
prepared by reaction of 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid with (RS)-benzofuran-4-carboxylic acid piperidin-3-ylamide.
Reaction SMILES: C([O:8][CH2:9][CH2:10][CH2:11][CH:12]1[O:16][C:15](=[O:17])[C:14]([OH:18])=[C:13]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)C1C=CC=CC=1>CO.[Pd]>[OH:18][C:14]1[C:15](=[O:17])[O:16][CH:12]([CH2:11][CH2:10][CH2:9][OH:8])[C:13]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C1OC(CCCOCc2ccccc2)C(c2ccccc2)=C1O
Agent: [Pd]
Solvent: CO
Product: O=C1OC(CCCO)C(c2ccccc2)=C1O
Yield: 95.9 %

Procedure:
5-(3-Benzyloxypropyl)-3-hydroxy-4-phenyl-2(5H)-furanone (65 mg) was dissolved in methanol (20 ml), and palladium black (20 mg) was added. Catalytic reduction was carried out in ordinary temperature and atmosphere. After completion of the reaction, the palladium black was filtered off and the methanol was distilled off under reduced pressure. The crude crystals thus obtained were recrystallized from chloroform to give 3-hydroxy-5-(3-hydroxypropyl)-4-phenyl-2(5H)-furanone (45 mg). m.p. 148°-150° C.