2-[5-(3-Ethynyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol → 2-[5-(3-Ethyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol

HRID 410545Notes

Reaction equation

HRID 410545 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C:25]([OH:28])([CH3:27])[CH3:26])=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)#[CH:2]>C(OCC)(=O)C.[Pd]>[CH2:1]([C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C:25]([OH:28])([CH3:27])[CH3:26])=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)[CH3:2]

Participants

4

Reactant 1

HCID 584563602-[5-(3-Ethynyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol

Product 1

HCID 584562962-[5-(3-Ethyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-olYield 63%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[5-(3-ethynyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol (19 mg, 0.047 mmol) in ethyl acetate (1 mL) was added Pd/C (10 wt %, 10.0 mg, 9.4 μmol, and the reaction vessel was then purged with H2 and stirred under an atmosphere of H2 (balloon) overnight. The catalyst was deactivated by addition of dichloromethane, then the mixture was filtered through Celite (ethyl acetate rinse) and concentrated in vacuo. The residue was then purified by preparative HPLC (50-90% CH3CN in 15 mM NH4HCO3(aq)) which provided 12 mg (0.029 mmol, 63%) of 2-[5-(3-ethyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol as a white solid. MS ESI: [M+H]+ m/z 409.1. 1H NMR (400 MHz, (CD3)2CO): δ 9.20 (s, 1H); 8.82 (d, J=4.9 Hz, 1H); 8.12 (s, 1H); 7.94 (s, 1H); 7.67 (s, 1H); 7.25-7.20 (m, 2H); 5.02 (s, 1H); 2.70 (q, J=7.6 Hz, 2H); 1.63 (s, 6H); 1.28 (t, J=7.6 Hz, 3H). rhSYK activity=+++

Workup

  1. customthe reaction vessel was then purged with H2
  2. additionThe catalyst was deactivated by addition of dichloromethane
  3. filtrationthe mixture was filtered through Celite (ethyl acetate rinse)
  4. concentrationconcentrated in vacuo
  5. customThe residue was then purified by preparative HPLC (50-90% CH3CN in 15 mM NH4HCO3(aq)) which

Sources & evidence

ORD record
ord-e07dd0a9441346f5895ad8d38c420c72
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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