Diisopropylethylamine → 2-[(S)-1-(2-Amino-5-cyano-6-methyl-pyrimidin-4-ylamino)-ethyl]-5-fluoro-3-pyridin-2-yl-3H-benzoimidazole-4-carbonitrile

HRID 243451Notes

Reaction equation

[NH2:1][C@H:2]([C:4]1[N:5]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[C:6]2[C:12]([C:13]#[N:14])=[C:11]([F:15])[CH:10]=[CH:9][C:7]=2[N:8]=1)[CH3:3].[NH2:22][C:23]1[N:28]=[C:27](Cl)[C:26]([C:30]#[N:31])=[C:25]([CH3:32])[N:24]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:22][C:23]1[N:28]=[C:27]([NH:1][C@H:2]([C:4]2[N:5]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[C:6]3[C:12]([C:13]#[N:14])=[C:11]([F:15])[CH:10]=[CH:9][C:7]=3[N:8]=2)[CH3:3])[C:26]([C:30]#[N:31])=[C:25]([CH3:32])[N:24]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-((S)-1-aminoethyl)-5-fluoro-3-pyridin-2-yl-3H-benzoimidazole-4-carbonitrile (0.085 g, 0.240 mmol), 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (0.057 g, 0.335 mmol) and DIPEA (0.17 mL, 0.960 mmol) in IPA (1.5 mL) was stirred at 80° C. in a sealed microwave tube for 16 hours. After cooling, the mixture was concentrated in vacuo and the residue was purified by chromatography (Si—PPC, gradient 0-8% 2M NH3/MeOH in DCM) to give 368 as an off white solid (0.064 g, 64%). LCMS (Method K): RT 2.87 min [M+H]+ 414.1. 1H NMR (DMSO, 400 MHz): δ 8.76-8.74 (1H, d), 8.02-7.97 (1H, t), 7.96-7.92 (1H, m), 7.58-7.54 (1H, m), 7.47-7.44 (1H, d), 7.15-7.10 (1H, t), 6.06-6.02 (1H, d), 5.42-5.35 (1H, m), 5.15-5.11 (2H, s), 2.32 (3H, s), 1.61-1.59 (3H, d)

Workup

temperatureAfter cooling
concentrationthe mixture was concentrated in vacuo
customthe residue was purified by chromatography (Si—PPC, gradient 0-8% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record: ord-4d11621e84594476bd79cc3ef97d7b41
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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