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

HRID 243440Notes

Reaction equation

Cl.Cl.[NH2:3][C@H:4]([C:6]1[N:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:8]2[C:14]([CH2:15][OH:16])=[C:13]([F:17])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH3:5].[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:3][C@H:4]([C:6]2[N:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:8]3[C:14]([CH2:15][OH:16])=[C:13]([F:17])[CH:12]=[CH:11][C:9]=3[N:10]=2)[CH3:5])[N:28]=[CH:27][N:26]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of [2-((S)-1-aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-yl]methanol dihydrochloride (159 mg, 0.45 mmol) in IPA (5 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (69 mg, 0.45 mmol) and DIPEA (228 μL, 1.33 mmol) and the reaction mixture heated at 80° 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 353 as a white solid (87 mg, 49%). 1H NMR 400 MHz δ (d6-DMSO): 7.78 (1H, s), 7.65-7.56 (2H, m), 7.55-7.38 (5H, m), 7.16 (2H, br s), 7.05 (1H, dd, J=10.6, 8.8 Hz), 5.15 (1H, quin, J=6.9 Hz), 4.51 (1H, t, J=5.0 Hz), 3.97 (2H, d, J=5.0 Hz), 1.43 (3H, d, J=6.9 Hz)

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-8b6c99b2b6c5466686a1592e9f50fb16
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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