Benzenesulfonyl chloride → 4-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1-(phenylsulfonyl)piperidin-4-ol

HRID 410563Notes

Reaction equation

HRID 410563 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([OH:30])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.C(N(CC)C(C)C)(C)C.[C:40]1([S:46](Cl)(=[O:48])=[O:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([OH:30])[CH2:25][CH2:26][N:27]([S:46]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)(=[O:48])=[O:47])[CH2:28][CH2:29]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 584561264-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-4-ol

Product 1

HCID 672579624-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1-(phenylsulfonyl)piperidin-4-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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) was dissolved in CH2Cl2 (1 mL). N,N-diisopropylethyl-amine (50 μL, 0.287 mmol) and benzenesulfonyl chloride (29 μL, 0.230 mmol) were added sequentially. The solution was stirred overnight at room temperature, then concentrated in vacuo on a Genevac. The resultant residue was dissolved in DMSO and purified via HPLC (48-82% CH3CN:H2O) to provide 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1-(phenylsulfonyl)piperidin-4-ol. MS ESI: [M+H]+ m/z 576.1. 1H NMR (600 MHz, DMSO-d6) δ 10.21 (s, 1H), 8.80 (d, J=5.2 Hz, 1H), 7.93 (d, J=9.2 Hz, 2H), 7.75 (dd, J=8.7, 10.3 Hz, 2H), 7.73 (s, 1H), 7.65 (t, J=8.1 Hz, 1H), 7.43 (s, 1H), 7.25 (d, J=5.1 Hz, 1H), 7.12 (s, 1H), 6.10 (s, 1H), 3.54 (d, J=12.3 Hz, 1H), 2.58 (t, J=12.3 Hz, 2H), 2.54-2.37 (m, 1H), 2.28 (s, 3H), 2.08 (t, J=16.1 Hz, 2H), 1.80 (d, J=14.6 Hz, 2H). rhSYK activity=++

Workup

  1. concentrationconcentrated in vacuo on a Genevac
  2. dissolutionThe resultant residue was dissolved in DMSO
  3. custompurified via HPLC (48-82% CH3CN:H2O)

Sources & evidence

ORD record
ord-afcdc9e5b6494551ab6d292ac7457eee
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…