Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(3'-cyano-4'-methylbiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216944

반응식

HRID 216944 반응식
[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.Br[C:39]1[CH:40]=[CH:41][C:42]([CH3:47])=[C:43]([CH:46]=1)[C:44]#[N:45].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1)=[O:22])[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:39]2[CH:40]=[CH:41][C:42]([CH3:47])=[C:43]([C:44]#[N:45])[CH:46]=2)=[CH:9][CH:10]=1

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 129940045-Bromo-2-methylbenzonitrileHCID 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 59568611(S)-tert-Butyl 4-(1-amino-3-(3'-cyano-4'-methylbiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate수율 78.6%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
85 °C

실험 절차

(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), 200 mg) and 5-bromo-2-methylbenzonitrile (80 mg) in acetonitrile (8 mL) were treated with an aqueous solution of sodium carbonate (2M, 0.387 mL) and nitrogen was bubbled through the mixture. 1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added and the mixture was heated at 85° C. for 18 h. The mixture was concentrated and purified by chromatography on silica eluting with 50 to 100% ethyl acetate/isohexane to afford the sub-titled compound (154 mg).

후처리

  1. customwas bubbled through the mixture
  2. addition1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added
  3. concentrationThe mixture was concentrated
  4. custompurified by chromatography on silica eluting with 50 to 100% ethyl acetate/isohexane

출처 및 근거

ORD 기록
ord-54ffee3264484572a254b1ec74e128d7
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193239B2

연결된 노트

불러오는 중…