Water → HCID 86696709, compound

HRID 1774209Notes

Reaction equation

HRID 1774209 reaction equation
CC([O-])(C)C.[K+].CS(O[CH2:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][N:19]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:15][CH:14]=1)(=O)=O.[O:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:36]2[N:41]=[C:40]([C:42]3[CH:47]=[CH:46][NH:45][C:44](=[O:48])[CH:43]=3)[CH:39]=[CH:38][N:37]=2)[CH2:31][CH2:30]1.O>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].C1COCC1.ClCCl.CC#N>[O:48]=[C:44]1[CH:43]=[C:42]([C:40]2[CH:39]=[CH:38][N:37]=[C:36]([NH:35][CH:32]3[CH2:33][CH2:34][O:29][CH2:30][CH2:31]3)[N:41]=2)[CH:47]=[CH:46][N:45]1[CH2:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][N:19]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:15][CH:14]=1

Participants

9

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 86696649HCID 86696649, compoundHCID 86696710HCID 86696710, compound2×

Product 1

HCID 86696709HCID 86696709, compoundYield 23.3%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

KOt-Bu (180 mg, 1.6 mmol) and n-Bu4NI (37 mg, 0.1 mmol) were added to a mixture of tert-butyl 6-((methylsulfonyloxy)methyl)-1H-indole-1-carboxylate (0.8 mmol) and 4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (164 mg, 0.6 mmol) in anhydrous THF (15 mL). The resulting mixture was stirred at 70° C. under microwave irradiation for 2 hours. LC-MS showed the tert-butyl 6-(((methylsulfonyl)oxy)methyl)-1H-indole-1-carboxylate had disappeared. The reaction mixture was treated with water (20 mL) and diluted with dichloromethane. After removal of the insolubles by filtration, the filtrate was extracted with dichloromethane. The combined organic phase was dried with Na2SO4 and concentrated. The residue was purified with Combiflash (A: H2O including 0.5% NH3HCO3, B: CH3CN) to afford tert-butyl 6-((2-oxo-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-1(2H)-yl)methyl)-1H-indole-1-carboxylate (70 mg, 23% yield).

Workup

  1. customAfter removal of the insolubles
  2. filtrationby filtration
  3. extractionthe filtrate was extracted with dichloromethane
  4. dry with materialThe combined organic phase was dried with Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified with Combiflash (A: H2O including 0.5% NH3HCO3, B

Sources & evidence

ORD record
ord-404a2e07ebf44bc290ce0f376fc0f24c
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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