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

HRID 243431Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of (S)-1-(6-fluoro-7-methoxy-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (160 mg, 0.44 mmol) in IPA (3 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (72 mg, 0.47 mmol) and DIPEA (229 μL, 1.34 mmol) and the reaction mixture heated at 90° C. for 72 hours. 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 339 as a white solid (119 mg, 66%). 1H NMR 400 MHz δ (d6-DMSO): 7.80 (1H, s), 7.58 (1H, d, J=7.3 Hz), 7.55-7.47 (2H, m), 7.47-7.40 (3H, m), 7.39 (1H, dd, J=8.8, 4.0 Hz), 7.14 (2H, br s), 7.10 (1H, dd, J=12.2, 8.8 Hz), 5.24 (1H, quin, J=6.9 Hz), 3.32 (3H, d, J=0.7 Hz), 1.43 (3H, d, J=6.8 Hz), LCMS (Method K): RT=3.86 min, [M+H]+=404

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-fd1402bbaaee4311bb562626cfeb995d
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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