2-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl)propane-2-sulfonamide → 2-[5-(3-Amino-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide

HRID 410594Notes

Reaction equation

HRID 410594 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([C:21]2[S:25][C:24]([C:26]([S:29]([NH2:32])(=[O:31])=[O:30])([CH3:28])[CH3:27])=[N:23][CH:22]=2)[CH:7]=[C:8]([NH:10][C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][N:12]=2)[CH:9]=1)([O-])=O>CO>[NH2:1][C:4]1[CH:5]=[C:6]([C:21]2[S:25][C:24]([C:26]([S:29]([NH2:32])(=[O:31])=[O:30])([CH3:28])[CH3:27])=[N:23][CH:22]=2)[CH:7]=[C:8]([NH:10][C:11]2[N:16]=[C:15]([C:17]([F:19])([F:18])[F:20])[CH:14]=[CH:13][N:12]=2)[CH:9]=1

Participants

3

Reactant 1

HCID 584562412-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl)propane-2-sulfonamide

Product 1

HCID 584561682-[5-(3-Amino-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamideYield 62%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 2-[5-(3-nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide (Example 70, 200 mg, 0.409 mmol) in MeOH (10 mL) was added 3% Pt/0.6% V/C (53 mg, 0.008 mmol). The reaction was sealed, purged with hydrogen, and stirred under a hydrogen balloon at room temperature overnight. A small amount of starting material remained, so additional catalyst (50 mg) was added, and a fresh hydrogen balloon was placed on the reaction. After another 24 h at room temperature, the starting material had been consumed. The reaction was diluted with MeOH, gently heated to dissolve any precipitated product, and filtered through Celite. The filtrate was evaporated, and flash chromatography of the residue (dry load, 20-100% ethyl acetate in hexanes) afforded 2-[5-(3-amino-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide (116 mg, 62%) as an off-white solid. MS ESI: [M+H]+ m/z 459.0. 1H NMR (500 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.78 (d, J=4.9, 1H), 7.87 (s, 1H), 7.37 (s, 1H), 7.22 (d, J=4.9, 1H), 7.03 (s, 2H), 6.89 (s, 1H), 6.53 (t, J=1.7, 1H), 5.28 (s, 2H), 1.78 (s, 6H). rhSYK activity=+++

Workup

  1. customThe reaction was sealed
  2. custompurged with hydrogen
  3. additionwas added
  4. customa fresh hydrogen balloon was placed on the reaction
  5. waitAfter another 24 h at room temperature
  6. customthe starting material had been consumed
  7. additionThe reaction was diluted with MeOH
  8. temperaturegently heated
  9. dissolutionto dissolve any precipitated product
  10. filtrationfiltered through Celite
  11. customThe filtrate was evaporated
  12. dry with materialflash chromatography of the residue (dry load, 20-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-95e0a9cca3bb478eb4f24b26efe35cc2
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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