Sodium hydride → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 448582

Reaction equation

HRID 448582 reaction equation
[H-].[Na+].[CH3:3][S:4]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH2:11][CH2:10]2)(=[O:6])=[O:5].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[CH:35]=[C:34](Cl)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.[Cl-].[Na+].O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[CH:35]=[C:34]([N:12]3[C:13]4[C:9](=[CH:8][C:7]([S:4]([CH3:3])(=[O:6])=[O:5])=[CH:15][CH:14]=4)[CH2:10][CH2:11]3)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27361365-(Methanesulfonyl)-2,3-dihydro-1H-indoleHCID 22309472tert-Butyl 4-[(6-chloropyrimidin-4-yl)amino]piperidine-1-carboxylate

Product 1

HCID 580741254-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 62.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of NaH (0.62 g, 15.5 mmol, 60% NaH) in 40 mL of DMF, 5-methanesulfonyl-2,3-dihydro-1H-indole (1.9 g, 9.63 mmol) was added and the mixture was stirred at room temperature for 30 minutes. 17a (3.09 g, 9.88 mmol) was added in DMF and the mixture was heated at 85° C. for 17 h. After cooling to room temperature, brine was added (200 mL) and the mixture was extracted with DCM (200 mL then 3×500 mL). The combined extracts were washed with brine (3×100 mL), dried, filtered and evaporated. The residue was purified by flash chromatography (eluent: 25 to 100% EtOAc in hexane with 0.1% triethylamine) to afford 2.83 g (62%) of 17b.

Workup

  1. temperaturethe mixture was heated at 85° C. for 17 h
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with DCM (200 mL
  4. washThe combined extracts were washed with brine (3×100 mL)
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography (eluent: 25 to 100% EtOAc in hexane with 0.1% triethylamine)

Sources & evidence

ORD record
ord-193c47e56d1b44f9927c0f14fe6990bf
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Linked notes

Loading…