Boron tribromide → 4-amino-6-[[(1S)-1-[6-fluoro-1-(3-hydroxycyclobutyl)benzimidazol-2-yl]ethyl]amino]pyrimidine-5-carbonitrile

HRID 243478Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:17]([CH:18]3[CH2:21][CH:20]([O:22]CC4C=CC=CC=4)[CH2:19]3)[C:16]3[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:17]([CH:18]3[CH2:21][CH:20]([OH:22])[CH2:19]3)[C:16]3[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 4-amino-6-{(S)-1-[1-(3-benzyloxycyclobutyl)-6-fluoro-1H-benzoimidazol-2-yl]ethylamino}pyrimidine-5-carbonitrile (0.05 g, 0.11 mmol) in DCM (3 mL) was cooled to 0° C. To this mixture was added boron tribromide (0.22 mL, 0.22 mmol) dropwise and the resultant mixture stirred at RT for 2 h. The reaction mixture was quenched with MeOH (2 mL) and concentrated in vacuo. The resulting yellow solid was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford 404 as an off-white glassy solid (50 mg, 99%). 1H NMR (DMSO-d6): δ 7.97-8.09 (3H, m), 7.74 (1H, dd, J=7.75, 4.8 Hz), 7.50 (2H, br s), 7.26-7.36 (1H, m), 5.67 (1H, qn, J=6.7 Hz), 4.70 (1H, qn, J=8.5 Hz), 3.96 (1H, m), 2.72-2.91 (2H, m), 2.55-2.72 (2H, m), 1.6 (3H, d, 7.2 Hz). LCMS (Method K): RT 2.36 min [M+H]+ 368

Workup

customThe reaction mixture was quenched with MeOH (2 mL)
concentrationconcentrated in vacuo
customThe resulting yellow solid was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record: ord-0958575720004d308edbe32f24d40dfe
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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