Diisopropylethylamine → 4-Amino-6-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-propylamino]-pyrimidine-5-carbonitrile

HRID 243441Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:13])[CH2:11][CH3:12])[N:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26](Cl)[N:25]=[CH:24][N:23]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26]([NH:13][C@H:10]([C:8]2[N:7]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:6]3[CH:20]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=2)[CH2:11][CH3:12])[N:25]=[CH:24][N:23]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)propylamine (62 mg, 0.23 mmol), 4-amino-6-chloro-5-cyanopyrimidine (36 mg, 0.23 mmol) and DIPEA (0.08 mL, 0.46 mmol) in IPA (2 mL) was heated for 6 h at 90° C. After cooling to RT, the volatiles were removed in vacuo and the resulting residue was purified by column chromatography (Si—PPC, gradient 0-5% 2M NH3/MeOH in EtOAc) to afford 358 as a white solid (70 mg, 79%). LCMS (Method K): RT 4.10 min [M+H]+ 388.1. 1H NMR (DMSO-d6, 400 MHz): δ 7.81 (1H, s), 7.68 (1H, dd, J=8.8, 4.9 Hz), 7.56-7.44 (6H, m), 7.16 (2H, br s), 7.07 (1H, ddd, J=9.8, 8.8, 2.5), 6.79 (1H, dd, J=8.9, 2.5), 5.29 (1H, dt, J=7.7, 6.2), 1.97 (1H, dqd, J=14.9, 7.5, 6.2), 1.87 (1H, dqd, J=14.9, 7.5, 6.2), 0.75 (3H, t, J=7.5)

Workup

temperatureAfter cooling to RT
customthe volatiles were removed in vacuo
customthe resulting residue was purified by column chromatography (Si—PPC, gradient 0-5% 2M NH3/MeOH in EtOAc)

Sources & evidence

ORD record: ord-016c6107a23446a9b90688ff9d419715
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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