Diisopropylethylamine → 4-Amino-6-[(S)-1-(7-cyanomethyl-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrile

HRID 243435Notes

Reaction equation

Cl.Cl.[NH2:3][C@H:4]([C:6]1[N:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:8]2[C:14]([CH2:15][C:16]#[N:17])=[C:13]([F:18])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH3:5].[NH2:25][C:26]1[C:31]([C:32]#[N:33])=[C:30](Cl)[N:29]=[CH:28][N:27]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:25][C:26]1[C:31]([C:32]#[N:33])=[C:30]([NH:3][C@H:4]([C:6]2[N:7]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:8]3[C:14]([CH2:15][C:16]#[N:17])=[C:13]([F:18])[CH:12]=[CH:11][C:9]=3[N:10]=2)[CH3:5])[N:29]=[CH:28][N:27]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of [2-((S)-1-aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-yl]acetonitrile dihydrochloride (100 mg, 0.27 mmol) in IPA (2 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (44 mg, 0.28 mmol) and DIPEA (139 μL, 0.82 mmol) and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue purified by prep HPLC (C18 phenomenex column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient) to give 345 as a white solid (119 mg, 66%). 1H NMR 400 MHz δ (d6-DMSO): 7.73 (1H, dd, J=8.8, 4.8 Hz), 7.67 (1H, d, J=7.2 Hz), 7.63-7.58 (1H, m), 7.56-7.45 (4H, m), 7.18 (1H, dd, J=10.6, 8.8 Hz), 7.14 (2H, br s), 5.22 (1H, quin, J=5.2 Hz), 3.38-3.21 (2H, m), 1.47 (3H, d, J=6.8 Hz), LCMS (Method K): RT=3.56 min, [M+H]+=413

Workup

concentrationThe reaction mixture was concentrated in vacuo
customthe resultant residue purified by prep HPLC (C18 phenomenex column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient)

Sources & evidence

ORD record: ord-fd53f1eeb4dd403c8d819299e4a8ef2c
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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