6-chloro-N-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[1,3,5]triazine-2,4-diamine → N-[(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-[1,3,5]triazine-2,4-diamine

HRID 243395Notes

Reaction equation

HRID 243395 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:14]3[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:13]=3[N:12]=2)[CH3:10])[N:5]=[C:4]([NH2:27])[N:3]=1>CCOC(C)=O.[Pd]>[F:26][C:23]1[CH:24]=[CH:25][C:13]2[N:12]=[C:11]([C@@H:9]([NH:8][C:6]3[N:5]=[C:4]([NH2:27])[N:3]=[CH:2][N:7]=3)[CH3:10])[N:15]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:14]=2[CH:22]=1

Participants

4

Reactant 1

HCID 866688846-chloro-N-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[1,3,5]triazine-2,4-diamine

Product 1

HCID 68157270N-[(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-[1,3,5]triazine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-N—[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[1,3,5]triazine-2,4-diamine (100 mg, 0.26 mmol) in EtOAc (10 mL) was added a slurry of 10% Pd/C (40 mg) in IMS (5 mL) and the reaction mixture stirred at RT under a hydrogen atmosphere for 18 h. The suspension was then filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (C18, gradient 20-55% MeOH in 0.5% TFA/H2O) then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH affording 267 as a colourless foam (42.3 g, 46%). LCMS (Method K): RT 3.14 min [M+H]+ 350.0. 1H NMR (DMSO-d6, 400 MHz, 80° C.): δ 7.87 (1H, s), 7.66 (1H, dd, J=8.8, 4.9 Hz), 7.60-7.56 (2H, m), 7.54-7.49 (3H, m), 7.08 (1H, bs), 7.04 (1H, ddd, J=9.8, 8.7, 2.5 Hz), 6.77 (1H, dd, J=9.0, 2.5 Hz), 6.28 (2H, bs), 5.23 (1H, quintet, J=7.1 Hz), 1.45 (3H, d, J=6.9 Hz)

Workup

  1. filtrationThe suspension was then filtered through a pad of Celite®
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by column chromatography (C18, gradient 20-55% MeOH in 0.5% TFA/H2O)
  4. washThe cartridge was washed with MeOH
  5. washthe product eluted with 0.5M NH3/MeOH affording 267 as a colourless foam (42.3 g, 46%)
  6. customRT 3.14 min [M+H]+ 350.0

Sources & evidence

ORD record
ord-6d05276043de40c6989506ae514cf532
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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