Diisopropylethylamine → 4-amino-6-[(S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamino]pyrimidine-5-carbonitrile

HRID 243469Notes

Reaction equation

[Br:1][C:2]1[C:7]2[N:8]([CH:14]3[CH2:16][CH2:15]3)[C:9]([C@@H:11]([NH2:13])[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][C:3]=1[F:17].[NH2:18][C:19]1[C:24]([C:25]#[N:26])=[C:23](Cl)[N:22]=[CH:21][N:20]=1.CCN(C(C)C)C(C)C>CC(O)C.CO>[NH2:18][C:19]1[C:24]([C:25]#[N:26])=[C:23]([NH:13][C@H:11]([C:9]2[N:8]([CH:14]3[CH2:15][CH2:16]3)[C:7]3[C:2]([Br:1])=[C:3]([F:17])[CH:4]=[CH:5][C:6]=3[N:10]=2)[CH3:12])[N:22]=[CH:21][N:20]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamine (80 mg, 0.27 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (41 mg, 0.27 mmol) and DIPEA (140 μL, 0.80 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane) to afford 395 as a white solid (86 mg, 77%). LCMS (Method K): RT 4.10 min [M+H]+ 415.95. 1H NMR (CDCl3, 400 MHz): δ 8.20 (1H, s), 7.56 (1H, dd, J=8.73, 4.57 Hz), 7.10-7.04 (1H, m), 6.27 (1H, d, J=7.81 Hz), 6.06-5.98 (1H, m), 5.32 (2H, s), 3.52-3.46 (1H, m), 1.68 (3H, d, J=6.75 Hz), 1.45-1.33 (3H, m), 1.20-1.14 (1H, m)

Workup

temperatureAfter cooling to RT
washThe cartridge was washed with MeOH
concentrationconcentrated in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-25d9a053dd8341678889d67511ea978c
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

Loading…