Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:21]1[CH:25]=[CH:24][O:23][CH:22]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].P([O-])([O-])(O)=O.[Na+].[Na+]>CN(C)C=O.O>[NH2:1][C:2]1[N:6]([C:7]2[C:8]([Cl:18])=[CH:9][C:10]([C:14]([F:17])([F:15])[F:16])=[CH:11][C:12]=2[Cl:13])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:21]1[CH:25]=[CH:24][O:23][C:22]=1[C:14]([F:17])([F:16])[F:15]
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccoc1
Agent: O=P([O-])([O-])O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccoc1C(F)(F)F
Temperature: 50 °C
Reaction time: 16 h

Procedure:
To a solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(furan-3-yl)pyrazole (0.5 g) in dimethylformamide (15 ml) and water (5 ml) was added sodium dithionite (0.112 g) and disodium hydrogen phosphate (0.067 g). The mixture placed in a 400 ml Parr vessel, which was evacuated, then charged with trifluoromethylbromide gas to 20 psi. The mixture was shaken and heated at 50° C., for 2.5 hours, then left at room temperature for 16 hours. The vessel was then evacuated, then charged with trifluoromethylbromide to 40 psi, then shaken and heated to 50° C. for a further 7 hours, then left at room temperature for 16 hours. Further sodium dithionite (0.120 g) and disodium hydrogen phosphate (0.080 g) was added, the vessel evacuated, then charged with trifluoromethylbromide to 40 psi, then shaken and heated to 50° C. as before for 9 hours, then left at room temperature for 48 hours. Further sodium dithionite (0.240 g) and disodium hydrogen phosphate (0.160 g) were added, the vessel was evacuated, then charged with trifluoromethylbromide to 45 psi, then shaken and heated to 50° C. as before for a further 9 hours. The mixture was filtered and then poured into ether (100 ml) and water (100 ml). The organic layer was separated, washed twice with water (50 ml), dried (Na2SO4), and evaporated. The residue was purified by column chromatography on silica gel (25 g) eluted with dichloromethane. Combination and evaporation of suitable fractions gave 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(2-trifluoromethylfuran-3yl)pyrazole as a white solid, m.p. 155-7° C.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][NH:6][CH2:7][CH:8]1[O:13][CH2:12][CH2:11][CH2:10][O:9]1)[CH3:2].C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:29][CH2:30][C:31](Cl)=[O:32]>O>[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][N:6]([CH2:7][CH:8]1[O:13][CH2:12][CH2:11][CH2:10][O:9]1)[C:31](=[O:32])[CH2:30][Cl:29])[CH3:2]
Reactant: O=C(Cl)CCl
Reactant: CCOC(CNCC1OCCCO1)OCC
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccccc1
Product: CCOC(CN(CC1OCCCO1)C(=O)CCl)OCC

Procedure:
N-(2,2-Diethoxyethyl)-N-(1,3-dioxan-2-ylmethyl)-amine (4 grams), benzene (100 ml), water (100 ml) and sodium carbonate (2 grams) are charged into a glass reaction vessel equipped with a mechanical stirrer and thermometer. The mixture is cooled to a temperature of 5° to 10° C and chloroacetyl chloride (1.5 ml) is added dropwise with stirring. After the addition is completed stirring is continued until the reaction mixture reaches room temperature. After this time the organic phase is separated from the aqueous phase and is washed with water. The washed solution is then dried over anhydrous magnesium sulfate, filtered and stripped of solvent under reduced pressure to yield the desired product N-(2,2-diethoxyethyl)-N-(1,3-dioxan-2-ylmethyl)-α-chloroacetamide as the residue.
Reaction SMILES: [CH2:1]([N:5]([CH2:7][C:8]([O:10][C@H:11]1[CH2:30][C@@:29]2([CH3:31])[C@@H:22]([CH2:23][CH2:24][C@@H:25]2[C:26](=[O:28])[CH3:27])[C@H:21]2[C@H:12]1[C@:13]1([CH3:33])[C@@H:18]([CH2:19][CH2:20]2)[CH2:17][C@@H:16]2[O:32][C@@H:15]2[CH2:14]1)=[O:9])[CH3:6])[CH2:2][CH2:3][CH3:4].[BrH:34]>C(Cl)(Cl)Cl>[Br:34][C@H:15]1[CH2:14][C@@:13]2([CH3:33])[C@@H:18]([CH2:19][CH2:20][C@@H:21]3[C@@H:12]2[C@@H:11]([O:10][C:8](=[O:9])[CH2:7][N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH3:6])[CH2:30][C@@:29]2([CH3:31])[C@H:22]3[CH2:23][CH2:24][C@@H:25]2[C:26](=[O:28])[CH3:27])[CH2:17][C@@H:16]1[OH:32]
Reactant: CCCCN(C)CC(=O)O[C@H]1C[C@]2(C)[C@@H](C(C)=O)CC[C@H]2[C@@H]2CC[C@H]3C[C@@H]4O[C@@H]4C[C@]3(C)[C@H]21
Reactant: Br
Solvent: ClC(Cl)Cl
Product: CCCCN(C)CC(=O)O[C@H]1C[C@]2(C)[C@@H](C(C)=O)CC[C@H]2[C@@H]2CC[C@H]3C[C@H](O)[C@@H](Br)C[C@]3(C)[C@H]21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 11β-(N-butyl-N-methylaminoacetoxy)-2α,3α-epoxy-5α-pregnan-20-one (1.6 g) and aqueous 47% hydrobromic acid (2 ml) in chloroform (100 ml) was stirred at room temperature for 1 hour. The solution was washed with dilute sodium bicarbonate solution and water, dried and evaporated in vacuo to give a foam. Crystallization from ethyl acetate-petroleum ether afforded title compound, m.p. 108°-110°, [α]D +95° (1.303 g).
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:22]=[CH:21][C:11]([C:12]([NH:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:13])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[NH2:23][CH2:24][C@@H:25]([C:27]1[CH:28]=[CH:29][C:30]([OH:38])=[C:31]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:32]=1)[OH:26]>>[CH2:19]([O:18][C:16](=[O:17])[CH2:15][NH:14][C:12](=[O:13])[C:11]1[CH:21]=[CH:22][C:8]([N:5]2[CH2:6][CH2:7][CH:2]([NH:23][CH2:24][C@H:25]([OH:26])[C:27]3[CH:28]=[CH:29][C:30]([OH:38])=[C:31]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:32]=3)[CH2:3][CH2:4]2)=[CH:9][CH:10]=1)[CH3:20]
Reactant: CS(=O)(=O)Nc1cc([C@@H](O)CN)ccc1O
Reactant: CCOC(=O)CNC(=O)c1ccc(N2CCC(=O)CC2)cc1
Product: CCOC(=O)CNC(=O)c1ccc(N2CCC(NC[C@H](O)c3ccc(O)c(NS(C)(=O)=O)c3)CC2)cc1

Procedure:
The title compound was prepared from ethyl {[4-(4-oxo-1-piperidineyl)benzoyl]amino}acetate (which was obtained in Example 161) and N-[5-((1R)-2-amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (which was obtained in Example 10) according to the procedure of Example 180 as a white solid; mp >140° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.20 (t, J=7.1 Hz, 3H), 1.20-1.35 (m, 2H), 1.75-1.90 (m, 2H), 2.50-2.90 (m, 5 H), 2.90 (s, 3H), 3.70-3.85 (m, 2H), 3.93 (d, J=5.8 Hz, 2H), 4.10 (q, J=7.1 Hz, 2H), 4.47 (dd, J=7.9, 4.4 Hz, 1H), 6.79 (d, J=8.3 Hz, 1H), 6.90-7.00 (m, 3H), 7.16 (d, J=2.0 Hz, 1H), 7.72 (d, J=8.9 Hz, 2H), 8.58 (t, J=5.8 Hz, 1H); MS (ES) m/z: 535.2 (MH+); HRMS Calcd. for C26H37N4O7S(MH+): 535.2221. Found: 535.2216.
Reaction SMILES: C([O:5][C:6]([C:8]1[N:9]([CH2:13][C:14](=[O:31])[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:19][CH:18]=2)[CH:10]=[CH:11][CH:12]=1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH2:23]([C:20]1[CH:21]=[CH:22][C:17]([O:16][CH2:15][C:14](=[O:31])[CH2:13][N:9]2[CH:10]=[CH:11][CH:12]=[C:8]2[C:6]([OH:7])=[O:5])=[CH:18][CH:19]=1)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCc1ccc(OCC(=O)Cn2cccc2C(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCCCCCCc1ccc(OCC(=O)Cn2cccc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
0.045 g (0.105 mmol) tert-butyl-1-[3-(4-octylphenoxy)-2-oxopropyl]pyrrole-2-carboxylate is dissolved in 10 ml absolute dichloromethane and mixed with 0.900 g (7.89 mmol) trifluoroacetic acid. After stirring at room temperature for 1 hour, the batch is concentrated to dryness on the rotary evaporator. Two dissolutions in toluene and respective concentration on the rotary evaporator leave as a crude product a brownish solid which is recrystallized from methanol and some water drops and yields the product as a beige solid.
Reaction SMILES: [C:1]1([CH2:8][OH:9])([CH2:6][OH:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.C(N(CC)CC)C.[S:17](Cl)([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:24][C:23]1[CH:25]=[CH:26][C:20]([S:17]([O:7][CH2:6][C:1]2([CH2:8][OH:9])[CH2:5][CH:4]=[CH:3][CH2:2]2)(=[O:19])=[O:18])=[CH:21][CH:22]=1
Reactant: OCC1(CO)CC=CC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC2(CO)CC=CC2)cc1
Temperature: 26 °C
Reaction time: 16 h
Yield: 39 %

Procedure:
To an ice-cooled solution of cyclopent-3-ene-1,1-diyldimethanol (44.0 g, 343 mmol), triethylamine (34.7 g, 343 mmol) and 4-dimethylaminopyridine (4.19 g, 34.3 mmol) in dichloromethane (2 L) was added tosyl chloride (58.9 g, 309 mmol) portionwise. The reaction mixture was warmed to 26° C. After 16 h, the mixture was concentrated, and the resulting residue was purified by flash column chromatography (30% ethyl acetate in petroleum ether)) to afford product as a brown solid (34 g, 35% yield).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[CH:16][CH:15]=[N:14]3)=[O:10])[CH:5]=[CH:4][CH:3]=1.Br.C([O-])([O-])=[O:23].[K+].[K+]>CS(C)=O>[CH3:1][C:2]1[N:7]=[C:6]([C:8](=[O:23])[C:9]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[CH:16][CH:15]=[N:14]3)=[O:10])[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cccc(CC(=O)c2ccc3nccnc3c2)n1
Reactant: O=C([O-])[O-]
Agent: Br
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1cccc(C(=O)C(=O)c2ccc3nccnc3c2)n1
Temperature: 75 °C
Yield: 86 %

Procedure:
A stirred suspension of 6-(2-[6-methylpyridin-2-yl]-acetyl)quinoxaline (1.65 g, 6.3 mmole) in dry DMSO (50 ml) was heated to 70-80° C. (forming a yellow solution) and treated dropwise with aq. HBr (48%, 6 ml). After 2 h the solution was cooled, poured over ice-water and brought to pH 10 with K2CO3. Extraction with EtOAc (3×), drying over Na2SO4, filtration and concentration to dryness in vacuo gave the title compound as a crimson oil (1.5 g, 86%). m/z [ESMS]: 278 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:43]=[CH:42][C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:32])[CH:8]([CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)[N:9]=[C:10]([N:11]3[CH2:20][CH2:19][C:14]4(OCC[O:15]4)[CH2:13][CH2:12]3)[C:4]=2[CH:3]=1.Cl>O1CCOCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:43]=[CH:42][C:5]2[NH:6][C:7](=[O:32])[CH:8]([CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)[N:9]=[C:10]([N:11]3[CH2:12][CH2:13][C:14](=[O:15])[CH2:19][CH2:20]3)[C:4]=2[CH:3]=1
Reactant: COc1ccc(CN2C(=O)C(Cc3ccc4ccccc4c3)N=C(N3CCC4(CC3)OCCO4)c3cc(Cl)ccc32)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: O=C1CCN(C2=NC(Cc3ccc4ccccc4c3)C(=O)Nc3ccc(Cl)cc32)CC1
Temperature: 60 °C
Reaction time: 5 h
Yield: 21.2 %

Procedure:
7-Chloro-1-(4-methoxybenzyl)-3-(naphthalen-2-ylmethyl)-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.14 g, 0.24 mmol) was dissolved in 1,4-dioxane (4 mL), and concentrated aqueous hydrochloric acid (4 mL) was added. The reaction mixture was stirred at 60° C. for 5 hours, then the temperature increased to 80° C. for 2 hours. The solution was cooled, diluted with ethyl acetate, washed with saturated sodium bicarbonate solution, brine, dried with sodium sulfate, decanted and concentrated in the presence of silica. Chromatography provided 7-chloro-3-(naphthalen-2-ylmethyl)-5-(4-oxopiperidin-1-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (22 mg, 22% yield). ESI m/z measured 432.1487 [M+H]+. calculated 432.1479.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[N:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1)=[CH2:2].[Li][CH2:15]CCC.CI>C1COCC1>[CH3:15][C:13]1[N:9]([C:6]2[CH:5]=[CH:4][C:3]([CH:1]=[CH2:2])=[CH:8][CH:7]=2)[N:10]=[CH:11][N:12]=1
Reactant: C=Cc1ccc(-n2cncn2)cc1
Reactant: [Li]CCCC
Solvent: CI
Solvent: C1CCOC1
Product: C=Cc1ccc(-n2ncnc2C)cc1
Reaction time: 0.5 h
Yield: 46.5 %

Procedure:
To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (0.5 g, 2.9 mmol) in 10 mL of THF, was added n-BuLi (0.22 g, 3.5 mmol) at −78° C. and stirred for 30 min. To this methyl iodide in THF (0.50 g, 3.5 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH4Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure The crude compound was purified by flash chromatography (SiO2, 100-200 mesh, 40% EtOAc in Pet ether) afford the title compound as a pale brown liquid (250 mg, 46%): 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.55 (d, J=9 Hz, 2H), 7.42 (d, J=9 Hz, 2H), 6.76 (dd, J=18, 11 Hz, 1H), 5.83 (d, J=18 Hz, 1H), 5.38 (d, J=11 Hz, 1H), 2.55 (s, 3H); ESIMS m/z 186.13 ([M+H]+); IR (thin film) 1517, 1386, 1182, 847 cm−1.
Reaction SMILES: CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:23][C:24]([F:32])([F:31])[C:25]1([C:28](O)=[O:29])[CH2:27][CH2:26]1.[Cl:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][C:35]=1[N+:42]([O-:44])=[O:43]>C1COCC1>[Cl:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH:39][C:28]([C:25]2([C:24]([F:32])([F:31])[F:23])[CH2:27][CH2:26]2)=[O:29])=[CH:36][C:35]=1[N+:42]([O-:44])=[O:43]
Reactant: NCc1ccc(Cl)c([N+](=O)[O-])c1
Reactant: O=C(O)C1(C(F)(F)F)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Product: O=C(NCc1ccc(Cl)c([N+](=O)[O-])c1)C1(C(F)(F)F)CC1
Reaction time: 8 h

Procedure:
TBTU (0.44 g, 1.4 mmol) and TEA (0.43 mL, 3.1 mmol) are added to 1-trifluoromethyl-cyclopropanecarboxylic acid (0.19 g, 1.2 mmol) in THF (5 mL). After 10 min at rt 4-chloro-3-nitro-benzylamine (0.23 g, 1.2 mmol) is added to the reaction mixture and stirring is continued overnight. The mixture is concentrated, the crude is diluted with EtOAc and washed with sat.aq. NaHCO3-solution, water and brine. The organic layer is dried with Na2SO4 and concentrated.
Reaction SMILES: [C:1]1([CH:7]([C:11]([OH:13])=[O:12])[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[CH:18]1(O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>CCOCC.CN(C)C=O>[C:1]1([CH:7]([C:11]([OH:13])=[O:12])[C:8]([O:10][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OC1CCCCC1
Reactant: O=C(O)C(C(=O)O)c1ccccc1
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: O=C(O)C(C(=O)OC1CCCCC1)c1ccccc1

Procedure:
Phenylmalonic acid (13.5 g, 0.07 mol) in dry ether (40 mL) was treated with thionyl chloride (8.92 g, 5.4 mL, 0.07 mol) and one drop of N,N-dimethylformamide. The mixture was heated at 40°-50° C. for 3 hours. The clear solution was distilled under vacuum. The oily residue was redissolved in dry ether (40 mL), the solution was treated with cyclohexyl alcohol (0.075 mol), 7.9 mL) and refluxed for 2 hours. The mixture was worked up as before to give an oily product which crystallized on standing. Recrystallization was carried out from a benzene-petroleum ether (40°-60°) mixture to give a white crystalline product.
Reaction SMILES: [N:1]1([C:7](=[O:15])[CH2:8][N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+].[C:21](Cl)([Cl:23])=[O:22]>ClCCl>[N:1]1([C:7](=[O:15])[CH2:8][N:9]2[CH2:10][CH2:11][N:12]([C:21]([Cl:23])=[O:22])[CH2:13][CH2:14]2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: O=C(CN1CCNCC1)N1CCOCC1
Reactant: O=C(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C(Cl)N1CCN(CC(=O)N2CCOCC2)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To the solution of 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (0.5 g, 2.34 mmol) (Oakwood) in dichloromethane (15 mL) was added saturated sodium bicarbonate solution (15 mL). The reaction mixture was cooled to 0° C. and then followed by the dropwise addition of phosgene (20% in toluene, 2.22 mL, 4.21 mmol). The reaction mixture was allowed to warm up to room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was extracted with dichloromethane three times. The combined organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated to give crude 4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazine-1-carbonyl chloride as yellow oil and used for the next step without further purification.
Reaction SMILES: Cl.O.[NH:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.C(N(CC)CC)C.Cl[C:18]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[C:19]1([C:18]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:3]2[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=C1CCNCC1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=C1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Yield: 103.5 %

Procedure:
To a solution of 10.6 g (65.1 mmol) of 4-piperidone monohydrate hydrochloride and 20.0 g (198 mmol) of triethylamine in 150 ml of dimethylformamide, 18.1 g (65.1 mmol) of chlorotriphenylmethane were added at 60° C. in portions under stirring, followed by stirring for further 5 hours at the same temperature. After cooling, the triethylamine hydrochloride thus precipitated was filtered off and the filtrate was concentrated by evaporation under reduced pressure. To the residue, 150 ml of water were added and the resulting mixture was extracted with 300 ml of ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate. The solvent was concentrated by evaporation under reduced pressure, whereby 23.0 g (yield: 98.3%) of 1-triphenylmethyl-4-piperidone were obtained.
Reaction SMILES: CSC.[CH:4](=[N:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:22]1([CH:28]=[N+]=[N-])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>ClCCl.C(OC)(C)(C)C.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[C:5]1([CH:4]2[CH:28]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:11]2[S:12]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)(=[O:14])=[O:13])[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: [N-]=[N+]=Cc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)N=Cc2ccccc2)cc1
Agent: [Rh+2]
Agent: CC(=O)[O-]
Solvent: COC(C)(C)C
Solvent: ClCCl
Solvent: CSC
Product: Cc1ccc(S(=O)(=O)N2C(c3ccccc3)C2c2ccccc2)cc1

Procedure:
To a stirred solution of dimethylsulphide (7 μl, 0.1 mmol), rhodium (II) acetate (2 mg, 0.005 mmol) and N-benzylidene-toluene-p-sulphonamide (131 mg, 0.5 mmol; J. C. S. Perkin I (1981) 2435-2442) in dichloromethane (2 ml) was added phenyldiazomethane (prepared as in Example 36; 8.11 ml of a 0.074M solution in t-butylmethylether) over a period of 12 hours. Upon completion of the addition, the solvent was removed in vacuo and the residue chromatographed using silica gel eluting with 15:85 ethyl acetate:petrol to give the title compound as a 3:1 mixture of trans:cis isomers (144 mg, 82%).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:16]2[C:17](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:18](O)=[O:19])[C:8](=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:9](O)=[O:10]>C1COCC1>[OH:10][CH2:9][C:8]1[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=1[C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[CH2:18][OH:19]
Reactant: O=C(O)c1ccccc1-c1ccccc1C(=O)O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1ccccc1-c1ccccc1CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 81 %

Procedure:
Lithium aluminum hydride (12.60 grams, 0.332 mol) and THF (175 ml) were placed in a dry 500 ml three-necked round-bottomed flask fitted with a condenser, addition funnel, nitrogen inlet, and magnetic stirrer. The mixture was cooled with an ice bath and diphenic acid (40.00 grams, 0.165 mol) in THF (100 ml) was added dropwise to the stirring mixture. After the addition was complete, the flask was removed from the ice bath and allowed to warm to room temperature. The reaction mixture was heated at reflux for 2 hours, then stirred overnight at room temperature. After cooling the mixture with an ice bath, water (12.6 ml) was added dropwise, followed by the successive dropwise addition of 15% aqueous sodium hydroxide (12.6 ml) and water (38 ml). The resulting yellow mixture was warmed to room temperature, and the solids were separated by vacuum filtration. The filtrate was placed on a rotary evaporator to remove the solvent. The remaining brownish-yellow solid was recrystallized from toluene-hexane to give 28.60 grams (81% yield) of light brown solid product, melting point 105° to 108° C. 1H NMR (CDCl3): δ2.77 (br s, 2H, --OH); 3.95 (s, 4H, --CH2 --); 6.50-7.25 (m, 8H, aromatic).
Reaction SMILES: Br.[Br:2][C:3]1[CH:8]=[CH:7][N:6]2[CH2:9][C:10]([C:13]([F:16])([F:15])[F:14])(O)[N:11]=[C:5]2[CH:4]=1>C(O)C>[Br:2][C:3]1[CH:8]=[CH:7][N:6]2[CH:9]=[C:10]([C:13]([F:15])([F:16])[F:14])[N:11]=[C:5]2[CH:4]=1
Reactant: OC1(C(F)(F)F)CN2C=CC(Br)=CC2=N1
Agent: Br
Solvent: CCO
Product: FC(F)(F)c1cn2ccc(Br)cc2n1
Yield: 100.4 %

Procedure:
A mixture of 1.82 g of 7-bromo-2-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridin-2-ol hydrobromide and 10 ml of ethanol was stirred under heat-reflux for 1 day. The cooled reaction mixture was concentrated under reduced pressure, then water was added, and the mixture was extracted with ethyl acetate. The mixture was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 1.33 g of 7-bromo-2-trifluoromethylimidazo[1,2-a]pyridine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:15](=[O:16])[N:14]([CH2:17][C:18]([O:20]CC)=[O:19])[C:13]3[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=3[S:11][CH2:10]2)=[CH:5][CH:4]=1>O.C(O)(=O)C.S(=O)(=O)(O)O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[C:15](=[O:16])[N:14]([CH2:17][C:18]([OH:20])=[O:19])[C:13]3[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=3[S:11][CH2:10]2)=[CH:7][CH:8]=1
Reactant: CCOC(=O)CN1C(=O)C(c2ccc(OC)cc2)CSc2ccccc21
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc(C2CSc3ccccc3N(CC(=O)O)C2=O)cc1
Temperature: 25 °C
Reaction time: 19 h
Yield: 84.3 %

Procedure:
6.8 g of the product of Step A were dissolved in 136 ml of a mixture of equal parts of water, of acetic acid and sulfuric acid and the mixture was stirred for 19 hours at ambient temperature. 400 ml of water were added slowly with stirring for 10 minutes, and separation was effected to obtain 5.3 g of the expected product melting at 180° C. which was used as is for following step. An analytical sample was prepared by two successive crystallizations from 20 volumes of ether at reflux starting with 2.7 g of the acid to obtain 1.15 g of the product melting at 190° C. (approx.).
Reaction SMILES: C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[CH:14])=[CH:9][CH:8]=1.[CH3:15][C:16]([CH3:27])([CH2:25][F:26])[C:17](=[O:24])[CH2:18][N:19]1[CH:23]=[N:22][CH:21]=[N:20]1>O1CCCC1>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:17]([CH2:18][N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)([OH:24])[C:16]([CH3:27])([CH3:15])[CH2:25][F:26])=[CH:9][CH:8]=1
Reactant: C#Cc1ccc(Cl)cc1
Reactant: CC(C)(CF)C(=O)Cn1cncn1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(CF)C(O)(C#Cc1ccc(Cl)cc1)Cn1cncn1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 61.8 %

Procedure:
62 ml of butyl-lithium (15% strength in hexane, 0.1 mol) are added dropwise to 13.65 g (0.1 mol) of 4-chlorophenyl-acetylene in 50 ml of absolute tetrahydrofuran at 0° C., under nitrogen. The mixture is subsequently stirred at 0° C. for 15 minutes, and 18.5 g (0.1 mol) of 3,3-dimethyl-4-fluoro-1-(1,2,4-triazol-1-yl)-2-butanone in 30 ml of absolute tetrahydrofuran are then added dropwise. Thereafter, the reaction mixture is allowed to warm to room temperature and is subsequently stirred for 14 hours. It is concentrated by distilling off some of the solvent, the residue is taken up in ether and the mixture is washed neutral with water, dried over sodium sulphate and concentrated. The residue is recrystallized from diisopropyl ether. 19.9 g (61.9% of theory) of 1-(4-chlorophenyl)-4,4-dimethyl-5-fluoro-3-(1,2,4-triazol-1-ylmethyl)-1-pentin-3-ol or melting point 120° C. are obtained.