Diisopropylethylamine → 6-Bromo-N2-(1-(5,7-difluoroquinolin-6-yl)ethyl)pyrazine-2,3-diamine

HRID 1959769Notes

Reaction equation

[F:1][C:2]1[C:11]([CH:12]([NH2:14])[CH3:13])=[C:10]([F:15])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.Br[C:17]1[C:18]([NH2:24])=[N:19][CH:20]=[C:21]([Br:23])[N:22]=1.CCN(C(C)C)C(C)C>C(#N)C>[Br:23][C:21]1[N:22]=[C:17]([NH:14][CH:12]([C:11]2[C:2]([F:1])=[C:3]3[C:8](=[CH:9][C:10]=2[F:15])[N:7]=[CH:6][CH:5]=[CH:4]3)[CH3:13])[C:18]([NH2:24])=[N:19][CH:20]=1

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 1-(5,7-difluoroquinolin-6-yl)ethanamine (800 mg, 3.8 mmol), 3,5-dibromopyrazin-2-amine (972.0 mg, 3.8 mmol) and DIPEA (2.0 g, 15.4 mmol) in acetonitrile (50 mL) was heated with microwave irradiation at 180° C. for 45 min. The reaction mixture was concentrated under reduced pressure, diluted with water, extracted with DCM three times. The combined organic layers were separated and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (DCM/MeOH) to give the title compound as a yellow solid (508 mg, 35%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.95 (d, 1H), 8.46 (dd, 1H), 7.63 (d, 1H), 7.60 (dd, 1H), 7.11 (s, 1H), 7.08 (dd, 1H), 6.36 (bs, 2H), 5.45 (m, 1H), 1.70 (d, 3H). LCMS (method A): [MH]+=380/382, tR=5.03 min.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
additiondiluted with water
extractionextracted with DCM three times
customThe combined organic layers were separated
washwashed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by silica gel chromatography (DCM/MeOH)

Sources & evidence

ORD record: ord-4f55be124e664d77886cd0430c6f0a52
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410264B2

Reaction notes

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