Acetic Acid → 2-{1-[4-(6-phenyl-pyrazolo[1,5-a]pyrimidin-5-yl)-benzyl]-piperidin-4-yl}-3H-benzimidazol-5-carbonitrile

HRID 1851264Notes

Reaction equation

HRID 1851264 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[NH:9][C:10]3[CH:16]=[C:15]([C:17]#[N:18])[CH:14]=[CH:13][C:11]=3[N:12]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[C:26]1([C:32]2[C:33]([C:41]3[CH:48]=[CH:47][C:44]([CH:45]=O)=[CH:43][CH:42]=3)=[N:34][C:35]3[N:36]([N:38]=[CH:39][CH:40]=3)[CH:37]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.ClCCl.CN(C=O)C>[C:26]1([C:32]2[C:33]([C:41]3[CH:42]=[CH:43][C:44]([CH2:45][N:2]4[CH2:3][CH2:4][CH:5]([C:8]5[NH:9][C:10]6[CH:16]=[C:15]([C:17]#[N:18])[CH:14]=[CH:13][C:11]=6[N:12]=5)[CH2:6][CH2:7]4)=[CH:47][CH:48]=3)=[N:34][C:35]3[N:36]([N:38]=[CH:39][CH:40]=3)[CH:37]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydride2×HCID 687529322-Piperidin-4-yl-1h-benzoimidazole-5-carbonitrile hydrochloride saltHCID 866306654-(6-Phenylpyrazolo[1,5-a]pyrimidin-5-yl)benzaldehyde

Product 1

HCID 687516862-{1-[4-(6-phenyl-pyrazolo[1,5-a]pyrimidin-5-yl)-benzyl]-piperidin-4-yl}-3H-benzimidazol-5-carbonitrileYield 32.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

265 mg (1 mmol) 2-piperidine-4-yl-3H-benzimidazole-5-carbonitrile hydrochloride salt was dissolved in 5 mL methanol. 204 mg (2 mmol) triethylamine, 250 mg (0.84 mmol) 4-(6-phenylpyrazolo[1,5-a]pyrimidin-5-yl)benzaldehyde, 5 mL DMF, 12.5 mL dichloromethane and 131 mg (2.2 mmol) acetic acid were added and after 30 minutes stirring 355 mg (1.68 mmol) NaBH(OAc)3 was added. Additional NaBH(OAc)3 has been added after one, two, three and four hours (two equivalents each) and the reaction mixture has been stirred overnight at room temperature. Usual work-up and purification as described in previous experiments yields 138 mg of the desired material.

Workup

  1. additionwas added
  2. customUsual work-up and purification

Sources & evidence

ORD record
ord-743b974d833e43ab8dfec5863ae02371
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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