[(S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester → (S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamine

HRID 243167Notes

Reaction equation

HRID 243167 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:10]1[N:14]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:13]2[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:12]=2[N:11]=1)[CH3:9])(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[F:25][C:22]1[CH:23]=[CH:24][C:12]2[N:11]=[C:10]([C@@H:8]([NH2:7])[CH3:9])[N:14]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[C:13]=2[CH:21]=1

Participants

4

Reactant 1

HCID 68157166[(S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

Product 1

HCID 68158079(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamineYield 67.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of [(S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester (292 mg, 0.82 mmol) in TFA (4 mL) and DCM (12 mL) was stirred for 1 h at RT. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH, followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PPC, gradient 0-10% 2M NH3 in MeOH/DCM) to afford the title compound as a pale yellow oil (141 mg, 67%). Marfey's test: 76% de. LCMS (Method C): RT 1.34 min [M+H]+ 257. 1H NMR (CDCl3, 400 MHz): δ 8.80 (1H, dd, J=5.0, 1.5 Hz), 8.73-8.72 (1H, m), 7.81 (1H, ddd, J=8.0, 2.5, 1.5 Hz), 7.71 (1H, ddd, J=9.0, 4.5, 0.5 Hz), 7.56 (1H, ddd, J=8.0, 5.0, 1.0 Hz), 7.04 (1H, ddd, J=9.5, 9.0, 2.5 Hz), 6.75 (1H, ddd, J=8.5, 2.5, 0.5 Hz), 4.08 (1H, q, 6.5 Hz), 1.87 (2H, bs), 1.48 (3H, d, J=6.5 Hz).

Workup

  1. washThe cartridge was washed with MeOH
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (Si—PPC, gradient 0-10% 2M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-0074f936dfe54a90a5023ae516bc8be5
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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