Acetic Acid → HCID 45485761, compound

HRID 506178Notes

Reaction equation

HRID 506178 reaction equation
C([BH3-])#N.[Na+].[CH:5]([C:7]1[CH:8]=[CH:9][C:10]2[S:14][C:13]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([C:22]=3[NH:23][C:24]3[C:25]([CH3:33])=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][CH:28]=[CH:27]4)[C:20]#[N:21])=[CH:12][C:11]=2[CH:34]=1)=[O:6].[NH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.C(O)(=O)C.C(=O)(O)[O-].[K+]>CCO.C(Cl)Cl>[CH3:33][C:25]1[C:24]([NH:23][C:22]2[C:19]([C:20]#[N:21])=[CH:18][N:17]=[CH:16][C:15]=2[C:13]2[S:14][C:10]3[CH:9]=[CH:8][C:7]([CH2:5][N:35]4[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]4)=[CH:34][C:11]=3[CH:12]=2)=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[CH:28][NH:29]2.[OH:6][CH2:5][C:7]1[CH:8]=[CH:9][C:10]2[S:14][C:13]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([C:22]=3[NH:23][C:24]3[C:25]([CH3:33])=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][CH:28]=[CH:27]4)[C:20]#[N:21])=[CH:12][C:11]=2[CH:34]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 8082PiperidineHCID 516893Potassium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 86616832HCID 86616832, compound

Product 2

HCID 45485761HCID 45485761, compoundYield 57%HCID 68467654HCID 68467654, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

Sodium cyanoborohydride (8.0 mg, 0.13 mmol) was added in portions to a stirred mixture of 5-(5-formyl-1-benzothien-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile 227 (40 mg, 0.098 mmol), piperidine (10 mg, 0.12 mmol) and acetic acid (7.0 mg, 0.12 mmol) in EtOH (3.0 mL). The resulting mixture was stirred at r.t. overnight and diluted with CH2Cl2 (30 mL). Silica gel and potassium bicarbonate (20 mg) were added and the mixture was concentrated to give a solid residue which was purified by silica gel flash column chromatography (eluting with 3% MeOH in CH2Cl2) to give 26 mg (57%) of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[5-(piperidin-1-ylmethyl)-1-benzothien-2-yl]nicotinonitrile 228 as an off-white solid (MS: 478.3 (M+H); melting range: 180-182° C.; HPLC retention time: 7.1 min.), and 7 mg (18%) of 5-[5-(hydroxymethyl)-1-benzothien-2-yl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile 229 as an off-white solid (MS: 411.3 (M+H); melting range: 174-175° C., HPLC retention time: 8.6 min.(a)).

Workup

  1. concentrationthe mixture was concentrated
  2. customto give a solid residue which
  3. customwas purified by silica gel flash column chromatography (eluting with 3% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-31665d09d07140de8147a28f8a4cceeb
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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