Acetic Acid → 1-{4-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}ethanone

HRID 410564Notes

Reaction equation

HRID 410564 reaction equation
[C:1](O)(=[O:3])[CH3:2].[CH3:5][C:6]1[CH:7]=[C:8]([C:23]2[S:27][C:26]([C:28]3([OH:34])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:25][CH:24]=2)[CH:9]=[C:10]([NH:12][C:13]2[N:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][N:14]=2)[CH:11]=1.OC1C2N=NNC=2C=CC=1>CN(C)C=O>[OH:34][C:28]1([C:26]2[S:27][C:23]([C:8]3[CH:9]=[C:10]([NH:12][C:13]4[N:18]=[C:17]([C:19]([F:21])([F:22])[F:20])[CH:16]=[CH:15][N:14]=4)[CH:11]=[C:6]([CH3:5])[CH:7]=3)=[CH:24][N:25]=2)[CH2:29][CH2:30][N:31]([C:1](=[O:3])[CH3:2])[CH2:32][CH2:33]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 584561264-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-4-olHCID 178418300HCID 178418300, compound

Product 1

HCID 584563891-{4-Hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}ethanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of acetic acid (9 μL, 0.15 mmol) and Si-carbonyl diimidazole (266 mg, 0.287 mmol) was added a solution of 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-4-ol (Example 46, 50 mg, 0.115 mmol) and hydroxybenzotriazole (26 mg, 0.17 mmol) dissolved in N,N-dimethylformamide, and the resultant suspension was shaken in a Bohdan block overnight at room temperature. The reaction mixture was filtered and concentrated in vacuo, and the resultant residue was dissolved in DMSO and purified via HPLC (30-64% CH3CN:H2O) to provide 1-{4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-1-yl}ethanone. MS ESI: [M+H]+ m/z 478.1. 1H NMR (600 MHz, DMSO-d6) δ 10.23 (s, 1H), 8.81 (d, J=5.2 Hz, 1H), 7.95 (s, 2H), 7.44 (s, 1H), 7.26 (d, J=5.1 Hz, 1H), 7.14 (s, 1H), 6.30 (s, 1H), 4.25-3.99 (m, 1H), 3.73 (m, 1H), 3.41-3.34 (m, 1H), 3.07-2.97 (m, 1H), 2.47 (s, 3H), 2.32 (s, 3H), 2.25-2.14 (m, 1H), 1.93 (m, 2H), 1.75 (m, 1H). rhSYK activity=+++

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated in vacuo
  3. dissolutionthe resultant residue was dissolved in DMSO
  4. custompurified via HPLC (30-64% CH3CN:H2O)

Sources & evidence

ORD record
ord-ef1191be61374fd3aba96c3699775b7d
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…