Dichloromethane → 2-Fluoroethyl 4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate

HRID 1517331Notes

Reaction equation

HRID 1517331 reaction equation
C(N(C(C)C)CC)(C)C.Cl[C:11]([O:13][CH2:14][CH2:15][F:16])=[O:12].ClCCl.Cl.[CH3:21][S:22]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:34]1[CH:39]=[C:38]([O:40][CH:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)[N:37]=[CH:36][N:35]=1)[CH2:29][CH2:28]2)(=[O:24])=[O:23]>O>[CH3:21][S:22]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:34]1[N:35]=[CH:36][N:37]=[C:38]([O:40][CH:41]3[CH2:46][CH2:45][N:44]([C:11]([O:13][CH2:14][CH2:15][F:16])=[O:12])[CH2:43][CH2:42]3)[CH:39]=1)[CH2:29][CH2:28]2)(=[O:24])=[O:23]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10017Carbonochloridic acid, 2-fluoroethyl esterHCID 81531DiisopropylethylamineHCID 685639645-(Methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline hydrochloride

Product 1

HCID 252611442-Fluoroethyl 4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylateYield 38%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Diisopropylethylamine (178 μL, 0.997 mmol) and (2-fluoroethyl) chloroformate (33 μL, 0.350 mmol) were added at 0° C. to a dichloromethane (2 mL) suspension of the 5-(methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline hydrochloride (188 mg, 0.396 mmol) produced in Reference Example 27, and the mixture was stirred at room temperature for 80 minutes. To the reaction solution, water was added, followed by extraction with ethyl acetate three times. The obtained organic layer was washed with water and saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [(i) hexane:dichloromethane=1:1, V/V; (ii) hexane:ethyl acetate:dichloromethane=2:1:2-1:1:1-2:2:1, V/V; (iii) ethyl acetate:dichloromethane=1:1, V/V] to obtain the title compound as white powder (58.8 mg, yield: 38%).

Workup

  1. customproduced in Reference Example 27
  2. extractionfollowed by extraction with ethyl acetate three times
  3. washThe obtained organic layer was washed with water and saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography [(i) hexane:dichloromethane=1:1, V/V; (ii) hexane:ethyl acetate:dichloromethane=2:1:2-1:1:1-2:2:1, V/V; (iii) ethyl acetate:dichloromethane=1:1, V/V]

Sources & evidence

ORD record
ord-ae179a289dfb4e44a338910e800090a0
Source dataset
uspto-grants-2012_07
Patent number
US08232287B2

Reaction notes

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