Cyclopropylamine → 8-bromo-N-cyclopropyl-7-fluoro-3-methylquinoxalin-2-amine

HRID 1056131Notes

Reaction equation

[Br:1][C:2]1[C:3]([F:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[C:8]([CH3:13])=[N:7]2.CC[N:17]([CH:21]([CH3:23])[CH3:22])C(C)C.C1(N)CC1>CS(C)=O>[Br:1][C:2]1[C:3]([F:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:17][CH:21]1[CH2:23][CH2:22]1)[C:8]([CH3:13])=[N:7]2

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 5-bromo-3-chloro-6-fluoro-2-methylquinoxaline (600) (4.0 g, 14.52 mmol), DIEA (5.07 mL, 29.0 mmol) and cyclopropanamine (2.01 mL, 29.0 mmol) in DMSO (10 mL) in a sealed glass tube was heated in an oil bath at 85° C. for 3 h. The reaction mixture was poured onto 50 g of ice; the insoluble yellow solid was filtered, washed with 2×25 mL of water followed by 2×15 mL of hexanes. The yellow solid was collected and dried in a vacuum oven at 45° C. for 1 h to afford 3.1 g of the title compound. The filtrate was extracted with 2×50 mL of EtOAc. The combined organic extract was dried over MgSO4, filtered and concentrated. The crude residue was purified on a silica gel column (20-50% EtOAc in hexanes) affording 0.9 g of the title compound as a light orange crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (1H, dd, J=9.0, 6.1 Hz), 7.47 (1H, br.), 7.33 (1H, t, J=8.8 Hz), 3.06 (1H, m), 2.47 (3H, s), 0.81 (2H, m), 0.67 (2H, m). 19F NMR (377 MHz, DMSO-d6) δ ppm −104.62. m/z (ESI, +ve) 296/298 (M+H).

Workup

filtrationthe insoluble yellow solid was filtered
washwashed with 2×25 mL of water
customThe yellow solid was collected
customdried in a vacuum oven at 45° C. for 1 h

Sources & evidence

ORD record: ord-e017e3f719f14bbf9f385623e925fd34
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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