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

반응식

HRID 216982 반응식
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

참가 물질

6

반응물 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

생성물 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-ylcarbamate수율 81.5%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

반응 조건

온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-ea12d947de934818a81efa691e02a414
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193239B2

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