Trifluoroacetic acid → 4-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-sulfonamide

HRID 1040052Notes

Reaction equation

HRID 1040052 reaction equation
C(OC(=O)[NH:7][S:8]([N:11]1[CH2:16][CH2:15][C:14]([OH:40])([C:17]2[S:18][C:19]([C:22]3[CH:27]=[C:26]([NH:28][C:29]4[N:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=4)[CH:25]=[C:24]([CH3:39])[CH:23]=3)=[CH:20][N:21]=2)[CH2:13][CH2:12]1)(=[O:10])=[O:9])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:40][C:14]1([C:17]2[S:18][C:19]([C:22]3[CH:27]=[C:26]([NH:28][C:29]4[N:34]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:32]=[CH:31][N:30]=4)[CH:25]=[C:24]([CH3:39])[CH:23]=3)=[CH:20][N:21]=2)[CH2:15][CH2:16][N:11]([S:8]([NH2:7])(=[O:9])=[O:10])[CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 58456421Tert-butyl({4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}sulfonyl)carbamate

Product 1

HCID 584562224-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-sulfonamideYield 82.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl({4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}sulfonyl)carbamate (45 mg, 0.073 mmol) in DCM (0.7 mL) was added TFA (0.120 mL, 1.5 mmol) and the reaction was stirred at room temperature for 80 min, then more TFA (0.120 mL, 1.5 mmol) was added. After 90 min most volatiles were removed by N2 flow and vacuum. The residue was diluted with saturated aqueous NaHCO3 and ethyl acetate. The combined organic layers were dried and evaporated to give 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-1-sulfonamide (31 mg, 0.06 mmol, 82% yield). MS ESI: [M+H]+ m/z 515.2. 1H NMR (600 MHz, CDCl3): δ 8.59 (d, J=4.8 Hz, 1H); 7.87 (s, 1H); 7.81 (s, 1H); 7.25 (s, 1H); 7.02 (s, 1H); 7.00 (d, J=4.8 Hz, 1H); 3.59 (d, J=12 Hz, 2H); 3.14 (m, 2H); 2.34 (s, 3H); 2.26 (m, 2H); 1.94 (d, J=12 Hz, 2H). rhSYK activity=+++

Workup

  1. customAfter 90 min most volatiles were removed by N2 flow and vacuum
  2. additionThe residue was diluted with saturated aqueous NaHCO3 and ethyl acetate
  3. customThe combined organic layers were dried
  4. customevaporated

Sources & evidence

ORD record
ord-4109420b0c114a598a33a39cc3960e23
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

Loading…