Formaldehyde → HCID 178480502, compound

HRID 415082Notes

Reaction equation

HRID 415082 reaction equation
Cl.[NH:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[NH:11][C:12]([C:14]1[N:15]=[CH:16][NH:17][C:18]=1[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:24][C:23]=1[Cl:35])=[O:20])=[O:13].C=O.[CH3:38]CN(C(C)C)C(C)C.ClCCl>C1COCC1>[NH:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[NH:11][C:12]([C:14]1[N:15]=[CH:16][NH:17][C:18]=1[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:38])[CH2:31][CH2:30]2)=[CH:24][C:23]=1[Cl:35])=[O:20])=[O:13]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 178479721HCID 178479721, compound

Product 1

HCID 178480502HCID 178480502, compoundYield 55.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A flask was charged with N4-(1H-benzo[d]imidazol-2-yl)-N5-(2-chloro-4-(piperidin-4-yloxy)phenyl)-1H-imidazole-4,5-dicarboxamide hydrochloride (115 mg, 0.22 mmol), formaldehyde, 30% wt (0.030 mL, 4 mmol), DIEA (0.080 mL, 0.5 mmol), dichloromethane (20 mL) and THF (20 mL), and the reaction mixture was stirred for 15 hours at room temperature. The reaction mixture was filtered, and the precipitate was discarded. The product was purified by reverse phase HPLC using ammonium acetate and acetonitrile as eluent to afford 60 mg (55% yield) of N4-1H-benzimidazol-2-yl-N5-(2-chloro-4-{[1-(methyl)piperidin-4-yl]oxy}phenyl)-1H-imidazole-4,5-dicarboxamide. 1H-NMR (400 MHz, DMSO-d6): δ 8.06 (s, 1H), 7.91 (d, 9 Hz, 1H), 7.46 (s, br, 2H), 7.21 (d, 3 Hz, 1H), 7.12-7.03 (m, 3H), 4.44-4.42 (m, 1H), 2.61-2.50 (m, 2H), 2.20-2.17 (m, 5H), 1.96-1.89 (m, 2H), 1.67-1.61 (m, 2H). MS (EI): 494 (MH+).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customThe product was purified by reverse phase

Sources & evidence

ORD record
ord-3991de12a17541fb9da184f603d7eee0
Source dataset
uspto-grants-2012_01
Patent number
US08088767B2

Reaction notes

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