Diisopropylethylamine → 2-Amino-4-[1-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)-ethylamino]-pyrimidine-5-carbonitrile

HRID 243448Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 1-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)ethylamine (68 mg, 0.29 mmol), 2-amino-4-chloropyrimidine-5-carbonitrile (44 mg, 0.29 mmol) and DIPEA (147 μL, 0.86 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 18 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 50-100% EtOAc in cyclohexane) followed by trituration from EtOAc to afford 365 as an off-white solid (47 mg, 46%). LCMS (Method K): RT 2.58 min [M+H]+ 357.09. 1H NMR (DMSO-d6, 400 MHz): δ 8.25 (1H, dd, J=4.76, 1.48 Hz), 8.14 (1H, dd, J=7.98, 1.47 Hz), 8.09 (1H, s), 7.72 (1H, d, J=7.41 Hz), 7.55-7.43 (5H, m), 7.32 (1H, dd, J=7.99, 4.77 Hz), 7.16-6.68 (2H, m), 5.55 (1H, m), 1.49 (3H, d, J=6.81 Hz)

Workup

temperatureAfter cooling to RT
washThe cartridge was washed with MeOH
concentrationconcentrated in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 50-100% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-552e98b697564e8aa5ea8dd98d48e7a6
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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