Diisopropylethylamine → 4-({2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-N-cyclopropylmorpholine-2-carboxamide

HRID 1435499Notes

Reaction equation

HRID 1435499 reaction equation
[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)[C:8]2[CH:19]=[CH:20][C:21]([S:23](Cl)(=[O:25])=[O:24])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH:27]1([NH:30][C:31]([CH:33]2[O:38][CH2:37][CH2:36][NH:35][CH2:34]2)=[O:32])[CH2:29][CH2:28]1.CCN(C(C)C)C(C)C>ClCCCl>[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)[C:8]2[CH:19]=[CH:20][C:21]([S:23]([N:35]3[CH2:36][CH2:37][O:38][CH:33]([C:31]([NH:30][CH:27]4[CH2:28][CH2:29]4)=[O:32])[CH2:34]3)(=[O:25])=[O:24])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 579372942-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chlorideHCID 57937375N-cyclopropylmorpholine-2-carboxamide

Product 1

HCID 236589434-({2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-N-cyclopropylmorpholine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (0.95 g, 2.35 mmol) was added to a solution of N-cyclopropylmorpholine-2-carboxamide (0.8 g, 2.6 mmol) (see following steps B and C for preparation) and DIPEA (0.82 mL, 4.7 mmol) in DCE (80 mL) at 80° C. The reaction mixture was stirred for 1 h and the solvent was concentrated. The product was purified by MPLC on silica gel using 60-90% EtOAc/Heptane to provide the title compound as white solid. Yield: 1.1 g (71%); 1H NMR (400 MHz, CDCl3) δ 0.39-0.54 (m, 2 H), 0.69-0.80 (m, 2 H), 1.49-1.69 (m, 3 H), 1.72 (s, 9 H), 1.75-1.86 (m, 3 H), 2.09 (t, J=10.84 Hz, 1 H), 2.2 (m, 3 H), 2.38-2.50 (m, 1 H), 2.61-2.71 (m, 1 H), 3.56 (d, J=11.91 Hz, 1 H), 3.67 (td, J=11.52, 1.95 Hz, 1 H), 3.91-4.06 (m, 3 H), 4.44 (d, J=7.03 Hz, 2 H), 6.58 (d, J=3.12 Hz, 1 H), 7.63-7.73 (m, 2 H), 8.04 (s, 1 H); MS (ESI) (M+H)+=538.8; Anal. Calcd for C26H36F2N4O4S+2.2 TFA: C, 46.25; H, 4.88; N, 7.10. Found: C, 46.26; H, 5.00; N, 6.95.

Workup

  1. concentrationthe solvent was concentrated
  2. customThe product was purified by MPLC on silica gel using 60-90% EtOAc/Heptane

Sources & evidence

ORD record
ord-4d33dc84bba44b5bb5c2bd6c2a44f724
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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