Cyclopropanecarbonyl chloride → HCID 67407387, compound

HRID 1949639Notes

Reaction equation

HRID 1949639 reaction equation
CO[C:3]([N:5]1[CH2:9][CH:8]([C:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH:7]2[N:20]([C:23](=[O:39])[CH:24]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:22][CH:6]12)=[O:4].[CH:40]1(C(Cl)=O)[CH2:42][CH2:41]1>C(Cl)Cl>[C:35]([O:34][C:32](=[O:33])[NH:31][CH:24]([CH:25]1[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1)[C:23]([N:20]1[CH2:21][CH2:22][CH:6]2[N:5]([C:3]([CH:40]3[CH2:42][CH2:41]3)=[O:4])[CH2:9][CH:8]([C:10]3[C:18]4[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=4)[NH:12][CH:11]=3)[CH:7]12)=[O:39])([CH3:37])([CH3:38])[CH3:36]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 674097574-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid methyl ester

Product 1

HCID 67407387HCID 67407387, compoundYield 109%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution containing amine 50 (197 mg, 0.41 mmol) in DCM (10 mL) was cooled to 0° C. TEA (73 mg, 0.72 mmol) was added followed by cyclopropanecarbonyl chloride (57 mg, 0.55 mmol) and the reaction mixture was warmed to ambient temperature. After 16 h, the reaction mixture was diluted with DCM and the resulting organic solution was washed successively with 1M HCl and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 247 mg of 57 as a yellow-colored oil which was used without further purification. 1H NMR (300 MHz, CDCl3), mixture of amide rotamers: δ8.70 (s, 0.5H), 8.60 (s, 0.5H), 8.25 (dd, J=5.4, 8.7 Hz, 0.5H), 8.10 (dd, J=5.1, 8.7 Hz, 0.5H), 7.03-6.99 (m, 1H), 6.97-6.89 (m, 1H), 6.80 (s, 1H), 5.38 (app t, J=9.3 Hz, 1H), 4.81 (d, J=5.1 Hz, 1H), 4.57-4.50 (m, 2H), 4.37 (app t, J=7.8 Hz, 1H), 4.24 (d, J=10.5 Hz, 1H), 4.16-4.04 (m, 2H), 3.93 (d, J=5.4 Hz, 1H), 3.81-3.73 (m, 1H), 3.54-3.40 (m, 2H), 2.41-2.37 (m, 1H), 1.79-1.60 (m, 8H), 1.45 (s, 9H), 1.21-1.09 (m, 6H), 1.04-1.01 (m, 3H), 0.91-0.86 (m, 1H) ppm. Mass spectrum, m/z [553.4] (M+H)+.

Workup

  1. temperaturethe reaction mixture was warmed to ambient temperature
  2. washthe resulting organic solution was washed successively with 1M HCl and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-2033738e817e4d20a1c4b18c1878a6ca
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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