Diisopropylethylamine → 4-amino-6-[[(1S)-1-(1-benzyl-6-fluoro-benzimidazol-2-yl)ethyl]amino]pyrimidine-5-carbonitrile

HRID 243468Notes

Reaction equation

[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C@@H:18]([NH2:20])[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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:20][C@H:18]([C:9]2[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:12]3[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=3[N:10]=2)[CH3:19])[N:25]=[CH:24][N:23]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-1-(1-benzyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamine (320 mg, 1.19 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (184 mg, 1.19 mmol) and DIPEA (1.06 mL, 5.95 mmol) in IPA (5 mL) was heated at 90° C. in a sealed vial overnight. The resultant mixture was allowed to cool to RT and then concentrated in vacuo. The residue was purified by column chromatography (silica gel, gradient 0-10% [2M NH3 in MeOH] in DCM) to afford 394 as a white solid (164 mg, 36%). LCMS (Method K): RT 3.58 min [M+H]+ 388.1 1H NMR (DMSO-d6, 400 MHz): δ 7.94 (1H, s), 7.69 (1H, d, J=7.9 Hz), 7.61 (1H, dd, J=8.9, 4.5 Hz), 7.13-7.28 (5H, m), 6.95-7.05 (3H, m), 5.65 (1H, qn, J=7.9 Hz), 5.46 (2H, q, J=9.91, 5.5 Hz), 3.12 (1H, d, J=5.5 Hz), 1.49 (3H, d, J=6.77 Hz)

Workup

temperatureto cool to RT
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (silica gel, gradient 0-10% [2M NH3 in MeOH] in DCM)

Sources & evidence

ORD record: ord-3b00df5b0ab44c74b1d17d5d93ee4a2f
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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