Potassium Carbonate → (S)-tert-butyl 4-(1-amino-3-(4'-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216914노트

반응식

HRID 216914 반응식
[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.[CH:40]([S:43]([C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1)(=[O:45])=[O:44])([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:34]2[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=2)=[CH:7][CH:6]=1.[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:49]2[CH:48]=[CH:47][C:46]([S:43]([CH:40]([CH3:42])[CH3:41])(=[O:45])=[O:44])=[CH:51][CH:50]=2)=[CH:7][CH:6]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 441193274-(Isopropylsulphonyl)benzeneboronic acidHCID 59568595(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

생성물 2

HCID 59568578(S)-tert-butyl 4-(1-amino-3-(4'-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateHCID 59568602(S)-tert-butyl 4-(1-amino-3-(4'-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
75 °C

실험 절차

(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iii), 1.0 g) in acetonitrile (5 mL) under nitrogen was treated with 4-fluorophenylboronic acid (0.135 g) and 4-(isopropylsulfonyl)phenylboronic acid (0.220 g) followed by aqueous potassium carbonate (2M, 1.93 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (13 mg). The mixture was stirred at 75° C. for 18 h. The reaction was evaporated, dissolved in dichloromethane, absorbed onto silica and to purified by chromatography on silica eluting with 50% ethyl acetate in isohexane and then 100% ethyl acetate to afford (S)-tert-butyl 4-(1-amino-3-(4′-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate and (S)-tert-butyl 4-(1-amino-3-(4′-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate as a mixture (0.620 g).

후처리

  1. customThe reaction was evaporated
  2. dissolutiondissolved in dichloromethane
  3. customabsorbed onto silica
  4. customto purified by chromatography on silica eluting with 50% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-dd4c8c20034542a180a7695d902dcd60
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193239B2

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