tert-Butanol → 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

HRID 1040051Notes

Reaction equation

HRID 1040051 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[C:8]([OH:12])([CH3:11])([CH3:10])[CH3:9].[CH3:13][C:14]1[CH:15]=[C:16]([C:31]2[S:35][C:34]([C:36]3([OH:42])[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)=[N:33][CH:32]=2)[CH:17]=[C:18]([NH:20][C:21]2[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=2)[CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[C:8]([O:12][C:6](=[O:7])[NH:5][S:2]([N:39]1[CH2:38][CH2:37][C:36]([OH:42])([C:34]2[S:35][C:31]([C:16]3[CH:17]=[C:18]([NH:20][C:21]4[N:26]=[C:25]([C:27]([F:30])([F:28])[F:29])[CH:24]=[CH:23][N:22]=4)[CH:19]=[C:14]([CH3:13])[CH:15]=3)=[CH:32][N:33]=2)[CH2:41][CH2:40]1)(=[O:4])=[O:3])([CH3:11])([CH3:10])[CH3:9]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 584561264-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-4-ol

Product 1

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)carbamateYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At 0° C., chlorosulfonyl isocyanate (14.95 μL, 0.172 mmol) in DCM (0.6 mL) was added to tert-butanol (16.47 μL, 0.172 mmol), after stirred for 30 min, 4-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidin-4-ol (50 mg, 0.115 mmol) and triethylamine (48.0 μL, 0.344 mmol) were added and the reaction aged for 20 min and ice bath removed. After stirred for 2 h, the crude reaction mixture was directly subject to column chromatography on silica gel (0-100% ethyl acetate in hexanes) to afforded 58 mg (0.094 mmol, 82%) 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. MS ESI: [M+H]+ m/z 615.1. 1H NMR (600 MHz, CDCl3): δ 8.64 (d, J=4.8 Hz, 1H); 7.87 (s, 1H); 7.84 (s, 1H); 7.31 (s, 1H); 7.03 (s, 1H); 7.01 (d, J=4.8 Hz, 1H); 3.81 (d, J=12 Hz, 2H); 3.47 (m, 2H); 2.36 (s, 3H); 2.25 (m, 2H); 2.00 (d, J=12 Hz, 2H); 1.50 (s, 9H). rhSYK activity=+++

Workup

  1. waitthe reaction aged for 20 min
  2. customice bath removed
  3. stirringAfter stirred for 2 h
  4. customthe crude reaction mixture

Sources & evidence

ORD record
ord-d1d5bade09204b0e9b8e7d6f66ca7a2d
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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