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

HRID 1517333Notes

Reaction equation

HRID 1517333 reaction equation
C(N(C(C)C)CC)(C)C.Cl[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].ClCCl.[CH3:24][S:25]([C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[N:33]([C:37]1[CH:42]=[C:41]([O:43][CH:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)[N:40]=[CH:39][N:38]=1)[CH2:32][CH2:31]2)(=[O:27])=[O:26]>O>[CH3:24][S:25]([C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[N:33]([C:37]1[N:38]=[CH:39][N:40]=[C:41]([O:43][CH:44]3[CH2:49][CH2:48][N:47]([C:11]([O:13][CH2:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)=[O:12])[CH2:46][CH2:45]3)[CH:42]=1)[CH2:32][CH2:31]2)(=[O:27])=[O:26]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 667096685-(Methylsulfonyl)-1-(6-(piperidin-4-yloxy)pyrimidin-4-yl)indoline

Product 1

HCID 68562874Benzyl 4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Diisopropylethylamine (93 μL, 0.53 mmol) and benzyl chloroformate (57 μL, 0.40 mmol) were added at 0° C. to a dichloromethane (5 mL) solution of the 5-(methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline (100 mg, 0.267 mmol) produced in Reference Example 28, and the mixture was stirred at room temperature for 1 hour. To the reaction solution, water was added, followed by extraction with dichloromethane three times. The obtained organic layer was washed with 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 (hexane:ethyl acetate=5:1-1:1, V/V). The obtained crude product was washed with diisopropyl ether to obtain the title compound as white powder (67.3 mg, yield: 50%).

Workup

  1. customproduced in Reference Example 28
  2. extractionfollowed by extraction with dichloromethane three times
  3. washThe obtained organic layer was washed with 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 (hexane:ethyl acetate=5:1-1:1, V/V)
  7. customThe obtained crude product
  8. washwas washed with diisopropyl ether

Sources & evidence

ORD record
ord-6521abd331fd4599bdb29d429a647ef8
Source dataset
uspto-grants-2012_07
Patent number
US08232287B2

Reaction notes

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