Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C([Mg]Cl)(C)C.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([CH:33]=[O:34])([CH2:30][CH2:31][CH3:32])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>C1COCC1>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([CH:33]([OH:34])[C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)([CH2:30][CH2:31][CH3:32])[CH2:26][CH2:25]1)=[O:23])([CH3:19])([CH3:20])[CH3:18]
Reactant: CCCC1(C=O)CCN(C(=O)OC(C)(C)C)CC1
Reactant: Ic1ccc2ccccc2n1
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: CCCC1(C(O)c2ccc3ccccc3n2)CCN(C(=O)OC(C)(C)C)CC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 19 %

Procedure:
To a solution of 2-iodoquinoline (670 mg, 2.6 mmol) in THF (10 mL) at 0° C. was slowly added isopropyl magnesium chloride (2.0 M in THF, 1.6 mL, 3.2 mmol). The reaction mixture was stirred at 0° C. for 30 minutes, then a solution of 4-formyl-4-propyl-piperidine-1-carboxylic acid tert-butyl ester (670 mg, 2.6 mmol) in THF (3 mL) was slowly added. The reaction mixture was stirred at 0° C. for 30 minutes, then warmed to room temperature, quenched with saturated aqueous NH4Cl solution, and extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (0% to 20% EtOAc in hexanes) to afford 190 mg (19%) of 4-(hydroxy-quinolin-2-yl-methyl)-4-propyl-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil.
Reaction SMILES: [H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][OH:17])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Br)=[CH:21][CH:20]=1.O>O1CCCC1>[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][O:17][CH2:23][C:22]2[CH:25]=[CH:26][C:19]([F:18])=[CH:20][CH:21]=2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: OCC1CCN(Cc2ccccc2)CC1
Reactant: Fc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Fc1ccc(COCC2CCN(Cc3ccccc3)CC2)cc1
Temperature: 25 °C
Yield: 59.2 %

Procedure:
A suspension of sodium hydride (60% dispersion in oil, 0.76 g, 19 mmol) in anhydrous tetrahydrofuran (38 mL) was stirred at room temperature under a nitrogen atmosphere. A solution of 1-benzyl-4-hydroxymethyl piperidine (3.82 g, 18.6 mmol) was added dropwise. After the addition was completed, the reaction mixture was stirred for 2 h. 4-Fluorobenzyl bromide (2.4 mL, 19 mmol) was added dropwise, then the reaction mixture was stirred for 72 h. Water (50 mL) was added and the resulting mixture was extracted three times with ethyl acetate. Drying over magnesium sulfate, filtration and concentration in vacuo gave an oil. Vacuum distillation (170° C. (Kugelrohr oven), 1.0 Torr) gave a colorless oil (3.45 g, 59% yield): 'H-NMR: 7.34-6.98 (m, 9H), 4.46 (s, 2H), 3.50 (s, 2H), 2.93-2.87 (m, 2H), 2.02-1.59 (m, 5H), 1.39-125 HR-MS Calcd.: 313.1478; Found: 313.1479; (m, 2H); Anal. Calcd.: for C20H24FNO: C,76.65, H,7.72, N,4.47; Found: C,77.27, H,7.69, N,4.45.
Reaction SMILES: [F:1][CH:2]([F:26])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[CH:4]=1.[CH3:27][S:28]([C:31]1[CH:32]=[C:33]([NH2:37])[CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29].Cl>>[CH3:27][S:28]([C:31]1[CH:32]=[C:33]([NH:37][C:12]([C:11]2[CH:10]=[N:9][N:8]3[C:3]([CH:2]([F:1])[F:26])=[CH:4][C:5]([C:15]4[CH:20]=[CH:19][C:18]([O:21][C:22]([F:24])([F:25])[F:23])=[CH:17][CH:16]=4)=[N:6][C:7]=23)=[O:13])[CH:34]=[CH:35][CH:36]=1)(=[O:29])=[O:30]
Reactant: CS(=O)(=O)c1cccc(N)c1
Reactant: O=C(O)c1cnn2c(C(F)F)cc(-c3ccc(OC(F)(F)F)cc3)nc12
Agent: Cl
Product: CS(=O)(=O)c1cccc(NC(=O)c2cnn3c(C(F)F)cc(-c4ccc(OC(F)(F)F)cc4)nc23)c1

Procedure:
The title compound was prepared from 7-difluoromethyl-5-(4-trifluoromethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.20) and 3-methanesulfonyl-phenylamine [commercially available as hydrochloride] according to general procedure II. Yellow solid. MS (ISP) 527.2 [(M+H)+]; mp 223° C.
Reaction SMILES: Cl.[CH:2]([N:4]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:6]([CH2:7][C@@H:8]([C:10]([O:12][CH3:13])=[O:11])[NH2:9])=[CH:5]1)=[O:3].C(N(CC)CC)C.[F:27][C:28]1[CH:38]=[CH:37][CH:36]=[CH:35][C:29]=1[CH:30]=[CH:31][C:32](O)=[O:33].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[F:27][C:28]1[CH:38]=[CH:37][CH:36]=[CH:35][C:29]=1[CH:30]=[CH:31][C:32]([NH:9][C@H:8]([C:10]([O:12][CH3:13])=[O:11])[CH2:7][C:6]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:4]([CH:2]=[O:3])[CH:5]=1)=[O:33]
Reactant: O=C(O)C=Cc1ccccc1F
Reactant: COC(=O)[C@@H](N)Cc1cn(C=O)c2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1cn(C=O)c2ccccc12)NC(=O)C=Cc1ccccc1F
Yield: 86 %

Procedure:
The same procedures as in Example 2 were carried out from the compound obtained in Example 29 (4.0 g), triethylamine (2.2 mL), 2-fluorocinnamic acid (2.6 g), WSC.HCl (3.0 g), and methylene chloride (100 mL), to give the captioned compound (4.8 g, 86%) as an oily product.
Reaction SMILES: [C:1]1([S:7]([OH:10])(=[O:9])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Cl-].[Ca+2].[F:14][C:15]1[CH:40]=[CH:39][C:18]([O:19][CH2:20][CH:21]2[CH2:25][CH2:24][CH:23](C#CCCOC(C3CCCCO3)=O)[O:22]2)=[CH:17][CH:16]=1>C(Cl)Cl>[C:1]1([S:7]([CH:23]2[O:22][CH:21]([CH2:20][O:19][C:18]3[CH:17]=[CH:16][C:15]([F:14])=[CH:40][CH:39]=3)[CH2:25][CH2:24]2)(=[O:9])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=S(=O)(O)c1ccccc1
Reactant: O=C(OCCC#CC1CCC(COc2ccc(F)cc2)O1)C1CCCCO1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: ClCCl
Product: O=S(=O)(c1ccccc1)C1CCC(COc2ccc(F)cc2)O1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To benzenesulfinic acid sodium salt (10.0g, 0.061 mol), 25% HCl was added dropwise with stirring until the solid dissolved. The reaction mixture was extracted (100 mL each, 3 times) with EtOAc, dried over Na2SO4 and concentrated to give benzenesulfonic acid (7.8 g, 90%). To a 100 mL round bottom with a magnetic stir bar, benzenesulfonic acid (4.61 g, 0.0324 mol), CaCl2(3.6 g, 0.0324 mol) and dry dichloromethane (30 mL) were added. The reaction mixture was cooled to 0° C. and (2S) (5RS)-2-(4-fluorophenoxymethyl)-5-hydroxy-tetrahydrofuran (4.6g, 0.0216 mol) in dry CH2Cl2 (20 mL) was added. The reaction mixture was stirred for 3 h and monitored by TLC (EtOAc-light petroleum ether 1:4, Rf=0.25). The reaction mixture was filtered through celite and washed with CH2Cl2 (3 times). The combined organic layer was washed with saturated aqueous Na2CO3, water brine and dried over Na2SO4 Solvent was removed under reduced pressure to afford the crude (2S) (5RS)-5-benzenesulfonyl-2-(4-fluorophenoxymethyl)tetrahydrofuran 14 which was crystallized from chloroform-hexane to give pure white solid, yield 6.8 g (93%), m.p. 102° C.-104°C. 1H NMR (200 MHz, CDCl3): δ 1.90-3.0 (m, 4 H), 3.85-5.0 (m, 4 H), 6.70-7.05 (m, 4 H), 7.45-7.72 (m 3 H), 7.77-8.0 (m, 2 H).
Reaction SMILES: C([O:3][C:4](=O)[CH:5]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=1)[CH2:6][C:7]1[C:8]([NH:20]C2C=CC=CC=2)=[N:9][C:10]([NH:13]C2C=CC=CC=2)=[N:11][CH:12]=1)C.S(=O)(=O)(O)O.[C:43](O)(=O)[CH3:44]>C(OCC)(=O)C>[CH3:36][O:35][C:29]1[CH:28]=[C:27]([CH:5]2[C:4](=[O:3])[N:20]([C:44]3[CH:43]=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:8]3[N:9]=[C:10]([NH:13][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[N:11]=[CH:12][C:7]=3[CH2:6]2)[CH:32]=[CH:31][C:30]=1[O:33][CH3:34]
Reactant: CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1
Reactant: CC(=O)O
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Product: COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1OC
Temperature: 80 °C

Procedure:
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(3,4-dimethoxy-phenyl)-propionic acid ethyl ester (470 mg, 0.94 mmol) (from Example 11b supra) in glacial acetic acid (3 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 80° C. overnight. After cooling, the reaction mixture was diluted with ethyl acetate (50 mL) and quenched with 2 N aqueous sodium hydroxide solution. The organic layer was separated and successively washed with water (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give the crude product which was crystallized from ethyl acetate-hexanes to give 6-(3,4-dimethoxy-phenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one as a light brown solid. (Yield 335 mg, 78.8%).
Reaction SMILES: [CH:1]1([C:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12]([C:17]4[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=4[O:24][CH3:25])=[N:11][C:10]=3[N:9]([CH3:26])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:34][CH2:35][OH:36]>CN(C)C=O>[CH:1]1([C:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH2:34][CH2:35][OH:36])=[CH:19][C:18]=4[O:24][CH3:25])=[N:11][C:10]=3[N:9]([CH3:26])[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COc1cc(O)ccc1-c1nc2c(c(C3CCCCC3)nn2C)c(=O)[nH]1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc(OCCO)ccc1-c1nc2c(c(C3CCCCC3)nn2C)c(=O)[nH]1
Temperature: 120 °C
Reaction time: 2 h
Yield: 35.6 %

Procedure:
To a 5 ml N,N-dimethylformamide solution of 150 mg (0.423 mmol) of the compound obtained in Example 36, 87.7 mg (0.635 mmol) of potassium carbonate and 33 μl (0.466 mmol) of 2-bromoethanol were added. The mixture was stirred at 100° C. for 1 hour and at 120° C. for 2 hours. Further, 16 μl (0.233 mmol) of 2-bromoethanol was added, and the mixture was stirred at 120° C. for 1 hour. Then, the reaction mixture was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate), and further recrystallized (toluene) to obtain 60 mg (36%) of the captioned compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[S:20])[CH2:10][N:9]=1.[OH-].[Na+].CO.Cl.[CH3:26][N:27]([CH2:29][CH2:30]Cl)[CH3:28]>O>[CH3:26][N:27]([CH3:28])[CH2:29][CH2:30][S:20][C:11]1[CH2:10][N:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[C:14]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=2[N:12]=1
Reactant: S=C1CN=C(c2ccccc2Cl)c2cc(Cl)ccc2N1
Reactant: CN(C)CCCl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CN(C)CCSC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 88.4 %

Procedure:
To a solution of 2.5 g of 1,3-dihydro-5-(2-chlorophenyl)-7-chloro-2H-1,4-benzodiazepine-2-thione in a solvent mixture comprising 10 ml of a 10% aqueous sodium hydroxide solution and 10 ml of methanol is added dropwise under ice cooling with stirring an aqueous solution of 1.7 g of N,N-dimethyl-2-chloroethylamine hydrochloride, and the resulting mixture is stirred at room temperature for 2.5 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The extract is rinsed with a 5% aqueous sodium hydroxide solution, washed with water and then dried over magnesium sulfate. The solvent is distilled off from the solution to obtain as the residue 2.7 g of an oily 2-(2-dimethylaminoethylthio)-5-(2-chlorophenyl)-7-chloro-3H-1,4-benzodiazepine. The oily product thus obtained is treated, according to usual procedure, with maleic acid and recrystallized from an isopropyl alcohol-acetone mixture to obtain 2.6 g of 2-(2-dimethylaminoethylthio)-5-(2-chlorophenyl)-7-chloro-3H-1,4-benzodiazepine maleate, m.p. 140°-142° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl:21][CH2:22][CH2:23][CH2:24][CH2:25]I>>[Cl:21][CH2:22][CH2:23][CH2:24][CH2:25][N:16]1[C:17](=[O:20])[CH2:18][CH2:19][N:13]([C:11](=[O:12])/[CH:10]=[CH:9]/[C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:14][CH2:15]1
Reactant: ClCCCCI
Reactant: O=C1CCN(C(=O)/C=C/c2ccc(Cl)c(Cl)c2)CCN1
Product: O=C(/C=C/c1ccc(Cl)c(Cl)c1)N1CCC(=O)N(CCCCCl)CC1

Procedure:
In analogy to the procedure described in example 5A, 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 1A]) and 1-chloro-4-iodobutane gave the title compound as orange solid. MS: 403.2 (MH+, 3Cl).
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:25][C:26]1[CH:27]=[C:28]([CH:36]=[CH:37][CH:38]=1)[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].O>C(#N)C>[C:32]([O:31][C:29]([C:28]1[CH:27]=[C:26]([CH:38]=[CH:37][CH:36]=1)[CH2:25][NH:2][C@H:3]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:30])([CH3:35])([CH3:33])[CH3:34]
Reactant: CC(C)(C)OC(=O)c1cccc(CBr)c1
Reactant: CC(C)(C)OC(=O)[C@@H](N)Cc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)c1cccc(CN[C@@H](Cc2ccccc2)C(=O)OC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56 %

Procedure:
To a solution of tert-butyl L-phenylalaninate hydrochloride (456 mg) in acetonitrile (8.00 mL) were added potassium carbonate (510 mg) and tert-butyl 3-(bromomethyl)benzoate (400 mg), followed by stirring at room temperature overnight. To the reaction suspension was added water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain tert-butyl N-[3-(tert-butoxycarbonyl)benzyl]-L-phenylalaninate (340 mg).
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.C[Si]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])(C)C.[Si:23]([O:30][C@H:31]1[C:36](=[CH2:37])[C@H:35]([CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[CH2:34][C:33](=O)[CH2:32]1)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>O1CCCC1>[Si:23]([O:30][C@H:31]1[C:36](=[CH2:37])[C@H:35]([CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:41])[CH3:42])[CH2:34]/[C:33](=[CH:17]\[C:18]([O:20][CH2:21][CH3:22])=[O:19])/[CH2:32]1)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]
Reactant: CCOC(=O)C[Si](C)(C)C
Reactant: C=C1[C@H](CO[Si](C)(C)C(C)(C)C)CC(=O)C[C@H]1O[Si](C)(C)C(C)(C)C
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: C=C1[C@H](CO[Si](C)(C)C(C)(C)C)C/C(=C\C(=O)OCC)C[C@H]1O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 59.1 %

Procedure:
n-Butyllithium (2.5 M in hexanes, 1.6 mL, 4 mmol) was added to a solution of diisopropylamine (0.56 mL, 4 mmol) in 5 mL of tetrahydrofuran at −78° C. After 30 minutes, ethyl trimethylsilylacetate (0.73 mL, 4 mmol) was added. After stirring 30 minutes, a solution of the compound of Example 16J (787 mg, 2 mmol) in 8 mL of tetrahydrofuran was added, followed by a rinse of 2 mL of tetrahydrofuran. After 2 hours, the reaction was quenched by the addition of 10 mL of saturated aqueous NH4Cl. After warming to ambient temperature, the mixture was poured into 100 mL of 20% NaCl, then extracted twice with 100 mL of tert-butyl methyl ether. The combined tert-butyl methyl ether extracts were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (300 mL of SiO2, elution with a gradient of 1:1 dichloromethane:hexanes to dichloromethane) to afford 538 mg (58% yield) of a ˜4:1 mixture of isomers favoring the title compound (538 mg, 58%).
Reaction SMILES: C(C1C=C(C(C)C)C=C(C(C)C)C=1S(NN=[C:21]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])(=O)=O)(C)C.Br[C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH:37]=[O:38]>>[CH:36]1([CH:37]([OH:38])[C:21]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:22][CH2:23][N:24]([CH3:25])[CH3:26])[CH2:39][CH2:40][CH2:41][CH2:34][CH2:35]1
Reactant: CC(C)c1cc(C(C)C)c(S(=O)(=O)NN=C(CCN(C)C)c2ccccc2)c(C(C)C)c1
Reactant: O=Cc1cccc(Br)c1
Product: CN(C)CC=C(c1ccccc1)C(O)C1CCCCC1

Procedure:
By using a method similar to that described in Example 22, but starting from β-dimethylaminopropiophenone 2,4,6-triisopropylbenzenesulphonylhydrazone (20 g) and 3-bromobenzaldehyde (5.6 cc), 1-(3-bromophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol (Z) hydrochloride (11.3 g) is obtained in the form of a white solid melting at 188° C. after recrystallisation from isopropanol (200 cc).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:11]=1[C:12]#[C:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[SH:30].C(=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C>[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[S:30][CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:11]=1[C:12]#[C:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1
Reactant: FC(F)(F)c1cccc(C#Cc2c(CCl)nc3ccccn23)c1
Reactant: Sc1ccccn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Product: FC(F)(F)c1cccc(C#Cc2c(CSc3ccccn3)nc3ccccn23)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 74.8 %

Procedure:
150 mg (0.421 mmol) of 2-(chloromethyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridine were dissolved in 5 ml of acetonitrile followed by the addition of 96 mg (0.842 mmol) of pyridine-2-thiol and 274 mg (0.842 mmol) of cesium carbonate. The solvent was stirred at r.t. for 2 h 30 min. The mixture was then poured into 40 ml of water, and then extracted 3 times with 15 ml of ethyl acetate. The collected organic phases were washed with 30 ml of a saturated sodium hydrogencarbonate solution, with 30 ml of brine and then were dried on Na2SO4 which was then removed by filtration and the obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, 80% to 70% of heptane, v/v). 129 mg (yield=74%) of 2-((pyridin-2-ylthio)methyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo-[1,2-a]pyridine were obtained as a beige solid. LC-MS: m/z=410 (MH+) UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.70 (d, J=6.7 Hz, 1H), 8.52-8.37 (m, 1H), 8.02 (s, 1H), 7.91 (d, J=7.6 Hz, 1H), 7.71 (dd, J=41.7, 4.5 Hz, 4H), 7.43 (s, 2H), 7.13 (d, J=1.1 Hz, 2H), 4.73 (s, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]([CH3:20])=[CH:18][C:17]3[C:16]([CH3:22])([CH3:21])[CH2:15][CH2:14][C:13]([CH3:24])([CH3:23])[C:12]=3[CH:11]=2)=[CH:6][C:3]=1[CH:4]=[O:5].I[CH3:26]>>[CH3:26][O:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]([CH3:20])=[CH:18][C:17]3[C:16]([CH3:22])([CH3:21])[CH2:15][CH2:14][C:13]([CH3:24])([CH3:23])[C:12]=3[CH:11]=2)=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: Cc1cc2c(cc1-c1ccc(O)c(C=O)c1)C(C)(C)CCC2(C)C
Reactant: CI
Product: COc1ccc(-c2cc3c(cc2C)C(C)(C)CCC3(C)C)cc1C=O
Yield: 80.5 %

Procedure:
In a similar maser to Example 10(b), by reaction of 2 g (6.2 mmol) of 2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde with 425 μl (6.8 mmol) of iodomethane, 1.68 g (88%) of the expected product are obtained.
Reaction SMILES: [CH2:1]([S:8]([NH:11][C:12]1[C:13](=[O:28])[N:14]([CH2:22][C:23]([O:25]CC)=[O:24])[C:15](=[O:21])[N:16]([CH2:18][O:19][CH3:20])[CH:17]=1)(=[O:10])=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>CO.O>[CH2:1]([S:8]([NH:11][C:12]1[C:13](=[O:28])[N:14]([CH2:22][C:23]([OH:25])=[O:24])[C:15](=[O:21])[N:16]([CH2:18][O:19][CH3:20])[CH:17]=1)(=[O:10])=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)Cn1c(=O)c(NS(=O)(=O)Cc2ccccc2)cn(COC)c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COCn1cc(NS(=O)(=O)Cc2ccccc2)c(=O)n(CC(=O)O)c1=O
Temperature: 25 °C

Procedure:
To a cooled (0° C.) suspension of the compound of Example 43 (10.0 g, 24 mmole) in methanol (50 mL) is added 1.0N NaOH (49 mL) over a period of 10 minutes. After the addition is complete, the solution is allowed to warm to room temperature over a period of 1.5 hours. The solvent is reduced under vacuum, residue diluted with water, and washed with ethyl acetate twice. The aqueous layer is acidified with 2.0N HCl to pH 1, extracted with ethyl acetate three times. The combined organic extracts are washed with water, then brine (twice). The solvent is removed to give the title compound.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2=[C:13]([N:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:20]3)[N:14]=[C:15]([C:17]#[N:18])[CH:16]=[C:11]2[C:10]([CH3:29])=[C:9]1[CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:31].[K+]>C(O)C.O>[CH2:1]([N:8]1[C:12]2=[C:13]([N:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:20]3)[N:14]=[C:15]([C:17]([NH2:18])=[O:31])[CH:16]=[C:11]2[C:10]([CH3:29])=[C:9]1[CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [OH-]
Reactant: Cc1c(C)n(Cc2ccccc2)c2c(N3CCc4ccccc4C3)nc(C#N)cc12
Agent: [K+]
Solvent: O
Solvent: CCO
Product: Cc1c(C)n(Cc2ccccc2)c2c(N3CCc4ccccc4C3)nc(C(N)=O)cc12
Yield: 83.3 %

Procedure:
1-Benzyl-7-(3,4-dihydro-1H-isoquinolin-2-yl)-2,3-dimethyl-1H-pyrrolo[2,3-c]pyridin-5-carbonitrile (300 mg, 0.76 mmol) prepared in Example 686 was diluted with a mixture of ethanol (7 ml) and water (1 ml). Potassium hydroxide (426 mg, 7.6 mmol) was added to the solution, which was then refluxed for 2 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried on anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/1, v/v) to give 260 mg of the titled compound as a white solid. (Yield: 84%)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]3[CH:19]=[C:18]([CH2:20][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[C:17](=[O:27])[C:8]4[CH:9]=[C:10]([OH:16])[CH:11]=[C:12]([S:13][C:14]=2[CH:15]=1)[C:7]3=4.Br[CH2:29][CH2:30][CH2:31][OH:32]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]3[CH:19]=[C:18]([CH2:20][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[C:17](=[O:27])[C:8]4[CH:9]=[C:10]([O:16][CH2:29][CH2:30][CH2:31][OH:32])[CH:11]=[C:12]([S:13][C:14]=2[CH:15]=1)[C:7]3=4
Reactant: O=c1c(Cc2cccnc2)cn2c3c(cc(O)cc13)Sc1cc(Br)ccc1-2
Reactant: OCCCBr
Product: O=c1c(Cc2cccnc2)cn2c3c(cc(OCCCO)cc13)Sc1cc(Br)ccc1-2
Yield: 53 %

Procedure:
According to Example 34, the compound (120 mg) produced in Example 54 was reacted with 3-bromopropanol (0.04 mL) to obtain the title compound (72 mg; 53%).