Cyclopropanecarbonyl chloride → (S)-1-(4-(cyclopropanecarbonyl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

HRID 1485719Notes

Reaction equation

HRID 1485719 reaction equation
C(N(CC)C(C)C)(C)C.[CH:10]1([N:13]2[CH:17]=[C:16]([C:18]3[CH:19]=[C:20]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28](=[O:30])[CH3:29])[C@@H:23]([CH3:31])[CH2:22][NH:21]4)[CH:15]=[N:14]2)[CH2:12][CH2:11]1.[CH:32]1([C:35](Cl)=[O:36])[CH2:34][CH2:33]1>ClCCCl>[CH:32]1([C:35]([N:21]2[C:20]3[C:25](=[CH:26][CH:27]=[C:18]([C:16]4[CH:15]=[N:14][N:13]([CH:10]5[CH2:12][CH2:11]5)[CH:17]=4)[CH:19]=3)[N:24]([C:28](=[O:30])[CH3:29])[C@@H:23]([CH3:31])[CH2:22]2)=[O:36])[CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 118079488HCID 118079488, compound

Product 1

HCID 118079473(S)-1-(4-(cyclopropanecarbonyl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanoneYield 72%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

N,N-Diisopropylethylamine (0.120 mL, 0.688 mmol) was added to a solution of (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (0.068 g, 0.229 mmol) and cyclopropanecarbonyl chloride (0.031 mL, 0.344 mmol) in 1,2-dichloroethane (2.0 mL), and the mixture stirred at 50° C. for 16 h. The reaction mixture was concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane) to afford (S)-1-(4-(cyclopropanecarbonyl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (0.060 g, 72%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.68-0.77 (m, 1 H), 0.83-1.02 (m, 5 H), 1.02-1.08 (m, 5 H), 1.87-2.04 (m, 1 H), 2.12 (s, 3 H), 3.33 (m, 1 H), 3.74 (tt, J=7.33, 3.81 Hz, 1 H), 4.61 (m, 1 H), 4.69-4.86 (m, 1 H), 7.37-7.57 (m, 2 H), 7.65 (s, 1 H), 7.85 (s, 1 H), 8.25 (s, 1 H). MS (ESI, pos. ion) m/z 365. [M+1]+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto afford an orange oil
  3. customThis material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-f423b04c6d5f4651bb66042fe13f13d1
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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