Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14]C)=[O:13])=[CH:7][CH:6]=2.[C:22]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)([OH:24])=[O:23]>>[C:22]([C:25]1[CH:30]=[CH:29][C:28]([C:2]2[C:3]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[N:4][C:5]3[C:10]([N:11]=2)=[CH:9][C:8]([C:12]([OH:14])=[O:13])=[CH:7][CH:6]=3)=[CH:27][CH:26]=1)([OH:24])=[O:23]
Reactant: O=C(O)c1ccc(B(O)O)cc1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Product: O=C(O)c1ccc(-c2nc3cc(C(=O)O)ccc3nc2-c2ccccc2)cc1
Yield: 19.6 %

Procedure:
The product was obtained via a Suzuki coupling reaction using the method previously shown in Example 20, Step 3, using methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (100 mg, 0.29 mmol, 1.00 equiv) and 4-carboxyphenylboronic acid (73 mg, 0.44 mmol, 1.50 equiv) as reactants. Purification by prep-TLC yielded 21 mg (19%) of 3-(4-carboxyphenyl)-2-phenylquinoxaline-6-carboxylic acid as a white solid.
Reaction SMILES: [Na].I[CH2:3][CH2:4][C:5]1[O:9][CH:8]=[N:7][C:6]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[C:16]([O:19]CC)(=[O:18])C>CS(C)=O>[C:10]1([C:6]2[N:7]=[CH:8][O:9][C:5]=2[CH2:4][CH2:3][C:16]([OH:19])=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CCOC(C)=O
Reactant: ICCc1ocnc1-c1ccccc1
Agent: [Na]
Solvent: CS(C)=O
Product: O=C(O)CCc1ocnc1-c1ccccc1
Temperature: 0 °C

Procedure:
Sodium cyannide (1.18 g) was dissolved in dimethyl sulfoxide (40 ml) and, under stirring, a solution of 5-(2-iodoethyl)-4-phenyloxazole (6.0 g) in dimethyl sulfoxide (20 ml) was added dropwise. The mixture was stirred for 2 hours, followed by addition of ice-water and extraction with ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was then distilled off and the residual crude 4-phenyloxazole-5-propionitrile was dissolved in a mixture of ethanol (40 ml) and 2N sodium hydroxide (40 ml) and the solution was refluxed under stirring for 2 hours. The reaction mixture was concentrated, diluted with water and washed with dichloromethane. The aqueous layer was adjusted to pH 2 with hydrochloric acid and the resulting crystalline precipitate was collected by filtration and recrystallized from ethyl acetate and then from ethanol to give 4-phenyloxazole-5-propionic acid as prisms, yield 0.95 g (21.8%), m.p. 142°-143° C.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]2[C:7]3[N:15]([CH2:16][CH2:17][CH2:18][CH:19](OC)[O:20]C)[C:14]([CH2:24][CH2:25][CH3:26])=[N:13][C:8]=3[CH:9]=[N:10][C:11]=2[CH:12]=1>C1COCC1.O>[Br:2][C:3]1[CH:4]=[CH:5][C:6]2[C:7]3[N:15]([CH2:16][CH2:17][CH2:18][CH:19]=[O:20])[C:14]([CH2:24][CH2:25][CH3:26])=[N:13][C:8]=3[CH:9]=[N:10][C:11]=2[CH:12]=1
Reactant: CCCc1nc2cnc3cc(Br)ccc3c2n1CCCC(OC)OC
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: CCCc1nc2cnc3cc(Br)ccc3c2n1CCCC=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.5 %

Procedure:
Concentrated hydrochloric acid (8 mL) was added to a mixture of 7-bromo-1-(4,4-dimethoxybutyl)-2-propyl-1H-imidazo[4,5-c]quinoline (57.0 g, 140.3 mmol) in THF (250 mL) and water (70 mL) and stirred overnight at ambient temperature. Additional concentrated hydrochloric acid (10 mL) was added and the reaction mixture was stirred for 4 hours. The reaction mixture was concentrated under reduced pressure and the residue was diluted with water and neutralized with saturated aqueous sodium bicarbonate solution. The mixture was diluted with 10% methanol in dichloromethane, the phases were separated, and the combined organics were dried over magnesium sulfate and concentrated under reduced pressure to afford 50.3 g of 4-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyraldehyde.
Reaction SMILES: Cl[C:2]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([Cl:12])=[CH:11][C:5]=2[S:4](=[O:14])(=[O:13])[N:3]=1.[CH3:15][CH:16]([NH2:23])[CH2:17][CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21]>>[Cl:12][C:10]1[CH:9]=[CH:8][C:6]2[NH:7][C:2]([NH:23][CH:16]([CH3:15])[CH2:17][CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21])=[N:3][S:4](=[O:14])(=[O:13])[C:5]=2[CH:11]=1
Reactant: O=S1(=O)N=C(Cl)Nc2ccc(Cl)cc21
Reactant: CC(C)CCCC(C)N
Product: CC(C)CCCC(C)NC1=NS(=O)(=O)c2cc(Cl)ccc2N1

Procedure:
Starting from 3,7-dichloro-4H-1,2,4-benzothiadiazine 1,1-dioxide (300 mg; 1.19 mmol) and 1,5-dimethylhexylamine (1 g; 7.73 mmol) and with the use of same procedure as in example 21 260 mg (63.5%) of the title compound was prepared; m.p. >220° C.; 1H-NMR (DMSO-d6) ppm; 10.50 (s, 1H, NH), 7.68 (d, 1H, H-8), 7.63 (dd, 1H, H-5), 7.25 (d, 1H, H-7), 7.1 (br, 1H, NH), 3.85 (q, 1H, CH), 1.5 (m, 4H ), 1.35 (m, 3H ), 1.15 (d, 3H, CH3), 0.85 (d, 6H, 2×CH3).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N+:12]([O-])=O)[CH:9]=[CH:8][C:7]=1[CH3:15])=[O:4]>C(OCC)(=O)C>[NH2:12][C:10]1[CH:9]=[CH:8][C:7]([CH3:15])=[C:6]([NH:5][C:3](=[O:4])[C:2]([F:1])([F:16])[F:17])[CH:11]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1NC(=O)C(F)(F)F
Solvent: CCOC(C)=O
Product: Cc1ccc(N)cc1NC(=O)C(F)(F)F
Reaction time: 12 h
Yield: 95 %

Procedure:
2,2,2-Trifluoro-N-(2-methyl-5-nitro-phenyl)-acetamide (3.91 g, 15.78 mmol) was taken up in ethyl acetate in a Paar vessel and flushed with argon. Palladium on carbon (400 mg) was added and the argon atmosphere was replaced with hydrogen at 50 psi. The vessel was shaken for 12 h. The hydrogen was then replaced with argon and the catalyst was removed by filtration through celite. The solvent was removed under reduced pressure to yield 3.27 g of the desired amine. C9H9F3N2O MS m/e=219.1 (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:6]2[N:7]=[C:8]([CH:20]([CH3:22])[CH3:21])[C:9]([CH:18]=O)=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:5]2=[CH:4][CH:3]=1.[OH-].[Na+].[CH3:25][C:26]([CH3:28])=[O:27]>>[Cl:1][C:2]1[N:6]2[N:7]=[C:8]([CH:20]([CH3:22])[CH3:21])[C:9](/[CH:18]=[CH:25]/[C:26](=[O:27])[CH3:28])=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:5]2=[CH:4][CH:3]=1
Reactant: CC(C)c1nn2c(Cl)ccc2c(-c2ccc(F)cc2)c1C=O
Reactant: CC(C)=O
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)/C=C/c1c(C(C)C)nn2c(Cl)ccc2c1-c1ccc(F)cc1
Reaction time: 8 h

Procedure:
To a solution of 7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[1,2-b]pyridazine-3-carbaldehyde (40 mg) was added 1N sodium hydroxide (19.3 mg) and acetone (0.425 mL) at ambient temperature. After 8 hours, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate=5-1) to give (3E)-4-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[1,2-b]pyridazin-3-yl]-3-buten-2-one as an yellow solid (33 mg).
Reaction SMILES: [C:1]1([C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClCCl.Br.[Br:25][CH2:26][CH2:27][NH2:28]>C(N(CC)CC)C>[Br:25][CH2:26][CH2:27][NH:28][C:7]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: NCCBr
Agent: Br
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: BrCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Reaction time: 48 h

Procedure:
272.1 g (976 mmol) of triphenylchloromethane, 800 ml of dichloromethane and 200 g (976 mmol) of 2-bromoethanamine hydrobromide are introduced into a 2-1 round bottom flask placed under nitrogen. The mixture is stirred and 300 ml of triethylamine are added dropwise and stirring is continued for 48 h. The triethylamine hydrochloride which precipitates is separated off, water is added to the filtrate, the organic phase is separated off and is washed with water and dried over sodium sulphate, and the solvent is evaporated off. An oil is obtained, which is purified by chromatography on a column of silica gel. After recrystallisation from a mixture of dichloromethane and cyclohexane 273.17 g of white solid are obtained. Melting point: 108°-109° C.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[N:4][CH:3]=1.O[CH2:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.Cl.C(O)(C)C>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[N:4][CH:3]=1
Reactant: COc1cc2c(Cl)cnnc2cc1O
Reactant: OCc1ccncc1
Agent: CCCCP(CCCC)CCCC
Agent: Cl
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: ClCCl
Solvent: CC(C)O
Product: COc1cc2c(Cl)cnnc2cc1OCc1ccncc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 122 %

Procedure:
The starting material, 4-chloro-6-methoxy-7-(4-pyridylmethoxy)cinnoline hydrochloride, was obtained by adding 4-chloro-7-hydroxy-6-methoxycinnoline (200 mg, 0.95 mmol), followed by 4-hydroxymethylpyridine (108 mg, 1 mmol) and 1,1′-(azodicarbonyl)dipiperidine (647 mg, 2.5 mmol), in portions, to a solution of tri(n-butyl)phosphine (640 μg, 2.5 mmol) in methylene chloride (6 ml). After stirring for 1 hour at ambient temperature, a solution of 7M hydrogen chloride in isopropanol (300 μl, 2.1 mmol) was added. The resulting solid was filtered off, washed with methylene chloride and ether to give 4-chloro-6-methoxy-7-(4-pyridylmethoxy)cinnoline hydrochloride as a solid (196 mg, 55%).
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]1[CH:19]=[CH:18][CH:17]=[CH:16][C:4]=1[CH2:5][S:6][C:7]1[NH:8][C:9]2[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=2[N:11]=1.ClC1C=CC=C(C(OO)=[O:29])C=1.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[CH3:1][N:2]([CH3:20])[C:3]1[CH:19]=[CH:18][CH:17]=[CH:16][C:4]=1[CH2:5][S:6]([C:7]1[NH:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]=1)=[O:29]
Reactant: CN(C)c1ccccc1CSc1nc2ccccc2[nH]1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CN(C)c1ccccc1CS(=O)c1nc2ccccc2[nH]1
Temperature: 0 °C
Yield: 58.6 %

Procedure:
2-(2-Dimethylaminobenzylthio)benzimidazole (4.8 g) was dissolved in a mixture of 40 ml of chloroform and 5 ml of methanol. After the solution was chilled to 0° C., 3.86 g of m-chloroperbenzoic acid (purity: 70%) was added portionwise. Ten minutes later, a saturated aqueous NaHCO3 solution was added to the reaction mixture, and the resulting mixture was extracted with chloroform. The chloroform solution was washed with saturated brine and then dried over anhydrous sodium sulfate. The chloroform was distilled off under reduced pressure and the residue was recrystallized from a mixture of chloroform and ether to obtain 2.97 g of 2-(2-dimethylaminobenzylsulfinyl)benzimidazole as a colorless crystalline product (m.p. 116° C., decomposed).
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]3[N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:20]=[CH:21][C:14]=23)=[C:8]([F:30])[CH:7]=1)=[O:4].[Cl:33]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.O.ClCCl>[Cl:33][C:21]1[C:14]2[C:15](=[N:16][CH:17]=[CH:18][C:13]=2[CH2:12][C:9]2[CH:10]=[CH:11][C:6]([NH:5][C:3](=[O:4])[C:2]([F:1])([F:31])[F:32])=[CH:7][C:8]=2[F:30])[N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:27])([CH3:28])[CH3:29])[CH:20]=1
Reactant: C[Si](C)(C)CCOCn1ccc2c(Cc3ccc(NC(=O)C(F)(F)F)cc3F)ccnc21
Reactant: O=C1CCC(=O)N1Cl
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: C[Si](C)(C)CCOCn1cc(Cl)c2c(Cc3ccc(NC(=O)C(F)(F)F)cc3F)ccnc21

Procedure:
550 mg (1.07 mmol) of 2,2,2-trifluoro-N-{3-fluoro-4-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)methyl]phenyl}acetamide and 143 mg (1.07 mmol) of N-chlorosuccinimide in 23 ml of carbon tetrachloride are heated at reflux for 20 min. After cooling, the mixture is diluted with water in dichloromethane and extracted. The organic phase is separated off, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (mobile phase: dichloromethane with increasing amounts of methanol).
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:17])=[N:4][S:5][C:6]=1[NH:7][C@H:8]([C:13]([O:15]C)=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11].[OH-].[Li+]>CO>[Br:1][C:2]1[C:3]([CH3:17])=[N:4][S:5][C:6]=1[NH:7][C@H:8]([C:13]([OH:15])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11]
Reactant: COC(=O)[C@H](CC(C)C)Nc1snc(C)c1Br
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: Cc1nsc(N[C@@H](CC(C)C)C(=O)O)c1Br
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To an ice cold solution of methyl N-(4-bromo-3-methylisothiazol-5-yl)-L-leucinate (11.7 g, 36.4 mmol) in methanol (300 mL) was slowly added over 10 min a 2.0 M aqueous lithium hydroxide solution (75 mL, 150 mmol). The resulting cloudy solution was stirred at room temperature for 3 hours. Most of the methanol was removed under reduced pressure and the resulting aqueous suspension was partitioned between EtOAc and water+90 ml of 10% HCl. The organic layer was washed once with water, dried over Na2SO4 and concentrated in vacuo to give N-(4-bromo-3-methylisothiazol-5-yl)-L-leucine as a white solid.
Reaction SMILES: [Br:1]Br.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:16][CH3:17])[C:13]=1[O:14][CH3:15])[C:8]([OH:10])=[O:9]>C(O)(=O)C>[Br:1][C:11]1[C:12]([O:16][CH3:17])=[C:13]([O:14][CH3:15])[C:5]([O:4][CH3:3])=[CH:6][C:7]=1[C:8]([OH:10])=[O:9]
Reactant: COc1cc(C(=O)O)cc(OC)c1OC
Reactant: BrBr
Solvent: CC(=O)O
Product: COc1cc(C(=O)O)c(Br)c(OC)c1OC
Temperature: 0 °C

Procedure:
A solution of bromine (100 mmol) in 100 mL of acetic acid is added dropwise to a solution of 3,4,5-trimethoxybenzoic acid (100 mmol) in 100 mL of acetic acid cooled by an ice water bath. After the red color of the resulting mixture is discharged, the mixture is poured onto 500 g of crushed ice. The resulting solid is collected by filtration, dried over P2O5 in vacuo, and recrystallized from Et2O to give the product as a pale yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[OH:39])[C:5]([N:7]([CH:33]([CH3:35])[CH3:34])[C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1[CH:16]1[CH2:25][CH2:24][C:23]2[CH:22]=[C:21]([O:26]C(=O)C(C)(C)C)[CH:20]=[CH:19][C:18]=2[CH2:17]1)=O.[CH:40]12[CH2:48][CH2:47][CH:44]([CH2:45][CH2:46]1)[CH2:43][N:42]([C:49](=O)[CH2:50]Cl)[CH2:41]2>>[CH:40]12[CH2:48][CH2:47][CH:44]([CH2:45][CH2:46]1)[CH2:43][N:42]([CH2:49][CH2:50][O:39][C:38]1[CH:37]=[CH:36][C:4]([CH2:5][N:7]([CH:33]([CH3:35])[CH3:34])[C:8]3[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=3[CH:16]3[CH2:25][CH2:24][C:23]4[CH:22]=[C:21]([OH:26])[CH:20]=[CH:19][C:18]=4[CH2:17]3)=[CH:3][C:2]=1[F:1])[CH2:41]2
Reactant: O=C(CCl)N1CC2CCC(CC2)C1
Reactant: COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(N(C(=O)c2ccc(O)c(F)c2)C(C)C)c1
Product: COc1ccc(C2CCc3cc(O)ccc3C2)c(N(Cc2ccc(OCCN3CC4CCC(CC4)C3)c(F)c2)C(C)C)c1
Yield: 12 %

Procedure:
Synthesized from pivalic acid 6-{2-[(3-fluoro-4-hydroxybenzoyl)isopropylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (25 mg) and 1-(3-azabicyclo[3.2.2]non-3-yl)-2-chloroethanone (19 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (3.3 mg) was obtained.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[CH2:41][CH2:42][CH2:43][C:44]([CH2:55][CH3:56])([O:47][Si:48]([CH2:53][CH3:54])([CH2:51][CH3:52])[CH2:49][CH3:50])[CH2:45][CH3:46].[H-].[Na+].C1OCCOCCOCCOCCOC1>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([O:24][CH2:41][CH2:42][CH2:43][C:44]([CH2:55][CH3:56])([O:47][Si:48]([CH2:53][CH3:54])([CH2:49][CH3:50])[CH2:51][CH3:52])[CH2:45][CH3:46])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Reactant: CCC(CC)(CCCBr)O[Si](CC)(CC)CC
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(CC)(CCCOC(C)(C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)O[Si](CC)(CC)CC
Yield: 100.2 %

Procedure:
1α,3β-Bis(tert-butyldimethylsilyloxy)-20-hydroxy-20-methylpregna-5,7,16-triene (100 mg, 0.175 mmol), 1-bromo-4-ethyl-4-(triethylsilyloxy)hexane (225 mg, 0.696 mmol), sodium hydride (60% in oil, 42 mg, 1.05 mmol), 15-crown-5 (38 mg, 0.173 mmol) and tetrahydrofuran (3 ml) were subjected to reaction using a procedure similar to that of Example 5(1) (reflux under heating for 3 hours), worked up and purified by column chromatography (hexane:toluene=2:1) to give the titled compound (143 mg, 100%) as a colorless solid.
Reaction SMILES: [BH4-].[Na+].[C:3]1([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:25]=[CH:24][C:19]([NH:20][N+]([O-])=O)=[CH:18][CH:17]=3)[CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.O.O.[Sn](Cl)Cl.[OH-].[Na+]>C(O)C>[C:3]1([N:9]2[CH2:10][CH2:11][N:12]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([NH2:20])=[CH:24][CH:25]=3)[CH2:13][CH2:14]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])Nc1ccc(CN2CCN(c3ccccc3)CC2)cc1
Agent: Cl[Sn]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1ccc(CN2CCN(c3ccccc3)CC2)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 49.1 %

Procedure:
A solution of sodium borohydride (63 mg, 1.68 mmol) in ethanol (1 ml) was added drop-wise to a stirred solution of 4-(4-phenylpiperazine-1-yl methyl)-nitro-aniline (1 g, 3.36 mmol) and tin (II) dichloride dihydrate (2.27 g, 10.10 mmol) in ethanol (20 ml) at 60° C. The resulting solution was stirred for 2 h after which the reaction was cooled to 0° C. and basified (pH>10) by the addition of sodium hydroxide (2M). The aqueous layer was extracted with dichloromethane (3×20 ml) and the combined organics washed with brine, then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate 1:1) to afford the title compound as a pale yellow solid (441 mg, 49%). HPLC retention time 5.82 min. Mass spectrum (ES+) m/z 268 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:5]=[C:6]([F:9])[C:7]=1F.BrC1C=C(F)C=C(F)C=1.BrC1C=C(F)C(F)=C(F)C=1>>[F:9][C:6]1[CH:5]=[C:4]([C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: Fc1cc(-c2ccsc2)cc(F)c1F
Agent: Fc1cc(Br)cc(F)c1F
Agent: Fc1cc(F)cc(Br)c1
Product: Fc1cc(F)cc(-c2ccsc2)c1

Procedure:
The same procedures set forth above in Example (1)(a) for synthesizing 3(3,4,5-trifluorophenyl)thiophene were followed, with the exception that 1-bromo-3,5-difluorobenzene was substituted for 1-bromo-3,4,5-trifluorobenzene as the 1-bromo-substituted fluorobenzene.
Reaction SMILES: C(O[C:5]1[CH:6]=[C:7]([CH:27]=[CH:28][CH:29]=1)[CH2:8][N:9]1[C:18]2[C:13](=[C:14]([CH2:23][CH:24]=[CH2:25])[C:15]([OH:22])=[C:16]([CH2:19][CH:20]=[CH2:21])[CH:17]=2)[CH2:12][CH2:11][C:10]1=[O:26])C=C.C1(CN2C3C(=C(CC=C)[C:43]([OH:50])=C(CC=C)C=3)CCC2=O)CCCCC1>>[CH2:19]([C:16]1[C:15]([OH:22])=[C:14]([CH2:23][CH:24]=[CH2:25])[CH:13]=[C:18]2[C:17]=1[CH2:12][CH2:11][C:10](=[O:26])[N:9]2[CH2:8][C:7]1[CH:27]=[CH:28][C:29]([O:50][CH3:43])=[CH:5][CH:6]=1)[CH:20]=[CH2:21]
Reactant: C=CCOc1cccc(CN2C(=O)CCc3c2cc(CC=C)c(O)c3CC=C)c1
Reactant: C=CCc1cc2c(c(CC=C)c1O)CCC(=O)N2CC1CCCCC1
Product: C=CCc1cc2c(c(CC=C)c1O)CCC(=O)N2Cc1ccc(OC)cc1

Procedure:
1-(3-allyloxybenzyl)-5,7-diallyl-3,4-dihydro-6-hydroxy-2(1H)-quinolinone and 1-(cyclohexylmethyl)-5,7-diallyl-3,4-dihydro-6-hydroxy-2(1H)-quinolinone.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16]C(C)(C)C)[CH2:13][C@H:12]1[C:21]1[O:22][C:23]([CH3:26])=[CH:24][N:25]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[C:21]1[O:22][C:23]([CH3:26])=[CH:24][N:25]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cnc([C@@H]2C[C@@H](OC(C)(C)C)CN2C(=O)OCc2ccccc2)o1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cnc([C@@H]2C[C@@H](O)CN2C(=O)OCc2ccccc2)o1
Reaction time: 16 h
Yield: 65.1 %

Procedure:
To a stirred solution of (2S,4R)-4-tert-butoxy-2-(5-methyl-oxazol-2-yl)-pyrrolidine-1-carboxylic acid benzyl ester (2 g, 5.59 mmol) in dichloromethane (15 mL) was added trifluoroacetic acid (1.57 mL) in dichloromethane (1:5) at 0° C. and the mixture was then stirred at room temp. for 16 h. The reaction mixture was neutralized with saturated sodium bicarbonate solution and extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude was then purified by column chromatography to give (2S,4R)-4-hydroxy-2-(5-methyl-oxazol-2-yl)-pyrrolidine-1-carboxylic acid benzyl ester (1.1 g, 65.1% yield) as an off white solid. MS calcd. for C16H19N2O4 [(M+H)+] 303.0, obsd. 303.4.
Reaction SMILES: C(OC([O:7][C@@H:8]([C@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:19]([O:21]CC=C)=[O:20])=[C:14]([CH2:17]O)[C@H:15]([CH3:16])[C@H:11]12)[CH3:9])=O)C=C.[S:27]1[CH:31]=[CH:30][N:29]2[CH:32]=[N:33][CH:34]=[C:28]12>>[OH:7][C@@H:8]([C@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:19]([O-:21])=[O:20])=[C:14]([CH2:17][N:33]3[CH:34]=[C:28]4[S:27][CH:31]=[CH:30][N+:29]4=[CH:32]3)[C@H:15]([CH3:16])[C@H:11]12)[CH3:9]
Reactant: C=CCOC(=O)O[C@H](C)[C@H]1C(=O)N2C(C(=O)OCC=C)=C(CO)[C@H](C)[C@H]12
Reactant: c1cn2cncc2s1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(Cn3cc4scc[n+]4c3)[C@H](C)[C@H]12
Yield: 25 %

Procedure:
The same procedure as in Example 1 was repeated except that 91 mg of allyl (1S,5R,6S)-6-[(1R)-1-allyloxycarbonyloxyethyl]-2-hydroxymethyl-1-methyl-1-carbapen-2-em-3-carboxylate and 155 mg of imidazo[5,1-b]thiazole were used, thereby obtaining 21.6 mg of the title compound.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1)[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1.[NH2:31][C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1.[BH3-]C#N.[Na+]>CO>[NH:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=[C:32]1[NH:31][CH2:27][C:26]1[CH:29]=[CH:30][C:23]([CH2:22][N:11]([CH2:10][C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH:12]2[C:21]3[N:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH2:15][CH2:14][CH2:13]2)=[CH:24][CH:25]=1
Reactant: O=Cc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Reactant: Nc1nc2ccccc2[nH]1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: c1cnc2c(c1)CCCC2N(Cc1ccc(CNc2nc3ccccc3[nH]2)cc1)Cc1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Using General Procedure A: To a stirred solution of 4-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzaldehyde (140 mg, 0.34 mmol) and 2-aminobenzimidazole (45 mg, 0.0.34 mmol) in MeOH (4 mL) was added NaBH3CN (64 mg, 1.1 mmol) and the mixture was stirred at room temperature for 20 hours. Purification of the crude yellow foam by column chromatography on silica gel (200:1:1—EtOAc:MeOH:NH4OH) followed by radial chromatography on silica gel (100:1:1—CH2Cl2:MeOH:NH4OH) afforded AMD9693 (26 mg, 15%) as a white solid. 1H NMR (CDCl3) δ 1.57–1.74 (m, 1H), 1.87–2.05 (m, 2H), 2.10–2.20 (m, 1H), 2.63–2.75 (m, 1H), 2.75–2.90 (m, 1H), 3.54 (s, 2H), 3.86 (d, 1H, J=16.8 Hz), 4.03–4.16 (m, 2H), 4.24–4.35 (m, 2H), 5.44 (br s, 1H), 6.88–6.91 (m, 4H), 7.10–7.19 (m, 7H), 7.42 (d, 1H, J=7.5 Hz), 7.54 (br s, 2H), 8.65 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ 21.16, 24.26, 29.10, 46.66, 48.40, 53.29, 60.62, 111.39 (br), 118.11 (br), 120.13, 121.81, 122.37, 127.22, 128.57, 133.86, 134.79, 137.41, 138.17, 143.78, 146.67, 155.56, 156.41, 157.20. ES-MS m/z 514.4 (M+H). Anal. Cald. for C32H31N7.0.8CH2Cl2.0.4C4H8O2: C, 66.98; H, 5.85; N, 15.90. Found: C, 67.14; H, 5.66; N, 15.87.