Trifluoroacetic acid → 1-(Piperidin-4-yl)-1-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol

HRID 410518Notes

Reaction equation

HRID 410518 reaction equation
[OH:1][C:2]([CH:26]1[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:10]=2)=[CH:7][N:8]=1)[CH3:3].C(O)(C(F)(F)F)=O>ClCCl>[NH:29]1[CH2:30][CH2:31][CH:26]([C:2]([C:4]2[S:5][C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][C:16]4[N:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][N:17]=4)[CH:10]=3)=[CH:7][N:8]=2)([OH:1])[CH3:3])[CH2:27][CH2:28]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 67431059Tert-butyl 4-{1-hydroxy-1-[5-(3-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}piperidine-1-carboxylate

Product 1

HCID 672566901-(Piperidin-4-yl)-1-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanolYield 54.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the product of Step 4 (18.2 mg, 0.033 mmol) in dichloromethane (1 mL) was added TFA (1.00 mL, 12.98 mmol) and the mixture was stirred at room temperature. The solvent was removed by evaporation and stripped with ethyl acetate. The residue was concentrated and dried under high-vacuum to afford 1-(piperidin-4-yl)-1-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol (Example 15(2), 12.5 mg, 0.018 mmol) as a TFA salt. APCI: [M+H]+ m/z 450.1. 1H NMR (500 MHz, DMSO-d6): δ 10.34 (1H, s), 8.86 (1H, d, J=4.89 Hz), 8.43 (2H, broad s), 8.14 (1H, s), 8.01 (1H, s), 7.67 (1H, d, J=8.10 Hz), 7.39 (1H, t, 7.88 Hz), 7.34-7.29 (2H, m), 3.18-3.02 (2H, m), 2.61-2.54 (2H, m), 1.92-1.77 (2H, m), 1.51 (3H, s), 1.55-1.41 (1H, m), 1.38-1.22 (1H, m). rhSYK activity=+++

Workup

  1. customThe solvent was removed by evaporation
  2. concentrationThe residue was concentrated
  3. customdried under high-vacuum

Sources & evidence

ORD record
ord-c077f76af17a435198ecb18342350499
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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