Ethyl chloroformate → HCID 178473353, compound

HRID 415079Notes

Reaction equation

HRID 415079 reaction equation
Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C:17]([C:19]1[N:20]=[CH:21][NH:22][C:23]=1[C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)=[CH:29][C:28]=1[CH3:40])=[O:25])=[O:18].C(N(C(C)C)CC)(C)C>C1COCC1.CC(N(C)C)=O>[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C:17]([C:19]1[N:20]=[CH:21][NH:22][C:23]=1[C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH:34]2[CH2:39][CH2:38][N:37]([C:2]([O:4][CH2:5][CH3:6])=[O:3])[CH2:36][CH2:35]2)=[CH:29][C:28]=1[CH3:40])=[O:25])=[O:18]

Participants

6

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 178428852HCID 178428852, compound

Product 1

HCID 178473353HCID 178473353, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

Ethyl chloroformate (0.1 mmol) in anhydrous THF was slowly added to a solution of N4-(1H-benzo[d]imidazol-2-yl)-N5-(2-methyl-4-(piperidin-4-yloxy)phenyl)-1H-imidazole-4,5-dicarboxamide (0.10 mmol) and diisopropylethylamine (0.20 mmol) in anhydrous DMA (5 mL) at 0° C. LCMS indicated that the reaction was complete in 5 minutes. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by preparative reverse phase HPLC (ammonium acetate/acetonitrile) to give 3.4 mg of ethyl 4-({4-[({4-[(1H-benzimidazol-2-ylamino)carbonyl]-1H-imidazol-5-yl}carbonyl)amino]-3-methylphenyl}oxy)piperidine-1-carboxylate. 1H-NMR (400 MHz, DMSO-d6): δ 12.19 (s, 1H), 8.13 (s, 1H), 7.48 (m, 2H), 7.11 (m, 2H), 6.96 (s, 1H), 6.88 (dd, 1H), 4.60 (m, 1H), 4.05 (m, 2H), 3.70 (m, 2H), 3.30 (m, 1H), 2.26 (s, 3H), 1.91 (m, 2H), 1.57 (m, 2H), 1.19 (t, 3H). MS (EI): 532.4 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe resulting residue was purified by preparative reverse phase HPLC (ammonium acetate/acetonitrile)

Sources & evidence

ORD record
ord-b844e691654a48d7a667dc21627455ab
Source dataset
uspto-grants-2012_01
Patent number
US08088767B2

Reaction notes

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