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

HRID 243466Notes

Reaction equation

HRID 243466 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]([C@H:18]3[CH2:21][C@H: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

4

Reactant 2

HCID 25134Boron tribromideHCID 178461971HCID 178461971, compound

Product 1

HCID 681581104-amino-6-[[(1S)-1-[6-fluoro-1-(3-hydroxycyclobutyl)benzimidazol-2-yl]ethyl]amino]pyrimidine-5-carbonitrileYield 157%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Amino-6-[(S)-1-[1-(trans-3-benzyloxycyclobutyl)-6-fluoro-1H-benzoimidazol-2-yl]ethylamino]-pyrimidine-5-carbonitrile (0.06 g, 0.13 mmol) in DCM (5 mL) cooled to 0° C. To this mixture was added boron tribromide (1M solution in DCM, 0.26 mL, 0.23 mmol) dropwise and the resulting 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 392 as a colourless glassy solid (75 mg, quantitative). LCMS (Method K): RT 2.41 min [M+H]+ 368.3. 1H NMR (DMSO-d6): δ 8.17 (1H, d, J=6.44 Hz), 8.07 (1H, s), 7.92 (1H, d, J=9.28 Hz), 7.81 (1H, dd, J=8.98, 4.77 Hz), 7.59 (2H, s), 7.41 (1H, t, J=9.27 Hz), 5.83-5.75 (1H, m), 5.49-5.39 (1H, m), 4.59-4.53 (1H, m), 3.16-2.97 (2H, m), 2.46-2.28 (2H, m), 1.67 (3H, d, J=6.81 Hz

Workup

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

Sources & evidence

ORD record
ord-9008f0301d8f4224a8a269af9b410d21
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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