Cyclopropanecarbonyl chloride → HCID 57937330, compound

HRID 1435509Notes

Reaction equation

HRID 1435509 reaction equation
[CH:1]1([C:4](Cl)=[O:5])[CH2:3][CH2:2]1.[C:7]([C:11]1[N:15]([CH2:16][CH:17]2[CH2:22][CH2:21][C:20]([F:24])([F:23])[CH2:19][CH2:18]2)[C:14]2[CH:25]=[CH:26][C:27]([S:29]([N:32]3[CH2:35][CH:34]([NH2:36])[CH2:33]3)(=[O:31])=[O:30])=[CH:28][C:13]=2[N:12]=1)([CH3:10])([CH3:9])[CH3:8].CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[C:7]([C:11]1[N:15]([CH2:16][CH:17]2[CH2:22][CH2:21][C:20]([F:23])([F:24])[CH2:19][CH2:18]2)[C:14]2[CH:25]=[CH:26][C:27]([S:29]([N:32]3[CH2:33][CH:34]([NH:36][C:4]([CH:1]4[CH2:3][CH2:2]4)=[O:5])[CH2:35]3)(=[O:31])=[O:30])=[CH:28][C:13]=2[N:12]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

6

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 57937360HCID 57937360, compound

Product 1

HCID 57937330HCID 57937330, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cyclopropane carbonylchloride (16 uL, 19 mg, 0.18 mmol) was added to a solution of 1-({2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)azetidin-3-amine (52 mg, 0.12 mmol) (see Example 102 for preparation) and DIPEA (41 uL, 31 mg, 0.24 mmol) in CH2Cl2 (5 mL). The reaction mixture was stirred for 4 h at room temperature, diluted with EtOAc (50 mL), washed with NaHCO3 (2×10 mL) and dried over Na2SO4. The crude product was purified by MPLC using Hex/EtOAc (1:4) on silica gel to give 60 mg (99%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 0.66-0.71 (m, 2 H), 0.71-0.77 (m, 2 H), 1.38-1.48 (m, 1 H), 1.51-1.64 (m, 2 H), 1.65 (s, 9 H), 1.68-1.86 (m, 4 H), 1.99-2.13 (m, 2 H), 2.19-2.35 (m, 1 H), 3.67 (dd, J=8.69, 6.15 Hz, 2 H), 4.00 (dd, J=8.8, 7.8 Hz, 2 H), 4.23-4.37 (m, 1 H), 4.53 (d, J=7.62 Hz, 2 H), 7.90 (dd, J=8.79, 1.76 Hz, 1 H), 8.03 (d, J=8.59 Hz, 1 H), 8.16 (d, J=1.17 Hz, 1 H); MS (ESI) (M+H)+=509.3; Anal. Calcd for C25H34F2N4O3S+1.20 TFA+0.1H2O (647.26): C, 50.85; H, 5.51; N, 8.66. Found: C, 50.81; H, 5.52; N, 8.43.

Workup

  1. washwashed with NaHCO3 (2×10 mL)
  2. dry with materialdried over Na2SO4
  3. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-99a9bee59d954f5d8dfc22b3fd942193
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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