Potassium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(6-methyl-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-3-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216982

Reaction equation

HRID 216982 reaction equation
C(=O)([O-])[O-].[K+].[K+].[NH2:7][C:8](=[O:43])[C@@H:9]([NH:26][C:27]([C:29]1([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28])[CH2:10][C:11]1[CH:16]=[CH:15][C:14](B2OC(C)(C)C(C)(C)O2)=[CH:13][CH:12]=1.Br[C:45]1[CH:46]=[C:47]2[CH2:53][N:52]([CH3:54])[C:51](=[O:55])[C:48]2=[N:49][CH:50]=1>O.C(#N)C>[NH2:7][C:8](=[O:43])[C@@H:9]([NH:26][C:27]([C:29]1([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:39])([CH3:41])[CH3:40])[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1)=[O:28])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:45]2[CH:46]=[C:47]3[CH2:53][N:52]([CH3:54])[C:51](=[O:55])[C:48]3=[N:49][CH:50]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 595685813-bromo-6-methyl-5H,6H,7H-pyrrolo[3,4-b]pyridin-7-oneHCID 59568592(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568557(S)-tert-Butyl 4-(1-amino-3-(4-(6-methyl-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-3-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateYield 81.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (176 mg) in water (2 mL) was added to (S)-tert-butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 329 mg), 3-bromo-6-methyl-5H-pyrrolo[3,4-b]pyridin-7(6H)-one (Example 32, step (ii), 144 mg) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (50 mg) in degassed acetonitrile (12 mL) at 20° C. under nitrogen. The resulting solution was stirred at 80° C. for 90 min. The reaction mixture was cooled and filtered and the filtrate diluted with ethyl acetate, and washed with water. The aqueous was then extracted with dichloromethane and the combined organics dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by chromatography on silica eluting with methanol/ethyl:acetate (15:85 to 25:75). Pure fractions were evaporated to dryness to afford the sub-titled compound (278 mg).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. additionthe filtrate diluted with ethyl acetate
  4. washwashed with water
  5. extractionThe aqueous was then extracted with dichloromethane
  6. dry with materialthe combined organics dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by chromatography on silica eluting with methanol/ethyl
  11. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-ea12d947de934818a81efa691e02a414
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Linked notes

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