Triethyl Phosphate → (1S,5S)-{1-[5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-(diethoxy-phosphoryloxy)-hexylcarbamoyl]-2,2-diphenyl-ethyl}-carbamic acid methyl ester

HRID 1516422

반응식

HRID 1516422 반응식
[CH3:1][O:2][C:3](=[O:44])[NH:4][C@H:5]([C:19](=[O:43])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][C@H:25]([N:28]([S:33]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1)(=[O:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:26][OH:27])[CH:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:45]([O:47][P:48](OCC)([O:50][CH2:51][CH3:52])=[O:49])[CH3:46].P(Cl)(OCC)(OCC)=O.[H-].[Na+]>O1CCCC1>[CH3:1][O:2][C:3](=[O:44])[NH:4][C@H:5]([C:19](=[O:43])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][C@H:25]([N:28]([S:33]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1)(=[O:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:26][O:27][P:48]([O:50][CH2:51][CH3:52])([O:47][CH2:45][CH3:46])=[O:49])[CH:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

참가 물질

6

반응물 4

HCID 6535Triethyl PhosphateHCID 13139Diethyl chlorophosphateHCID 24758Sodium hydrideHCID 513956Ppl-1002회

생성물 1

HCID 24778259(1S,5S)-{1-[5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-(diethoxy-phosphoryloxy)-hexylcarbamoyl]-2,2-diphenyl-ethyl}-carbamic acid methyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

The PL-100 compound (product of step F, 203 mg, 0.325 mmol) was dissolved in dry tetrahydrofuran (3 mL) and 0.2 mL triethylphosphate under N2 atmosphere. The mixture was stirred at this temperature for 15 min, followed by the addition of diethyl chlorophosphate (0.061 mL, 0.423 mmol). Sodium hydride (60% in mineral oil) (17 mg, 0.423 mmol) was added at 0° C. The solution was stirred for 1 h at 0° C. and 12 h at room temperature. 20 mL of Amberlite XAD-2 was added to the solution and the beads were thoroughly mixed with the solvent. To the mixture was added ice water 0.2 mL, and the THF evaporated off. The beads were then washed with distilled water 6 times 100 mL then extracted three times with ethyl acetate (30 mL). The combined phase was evaporated and the residue was dried under high vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexane (8/2), then EtOAc 100% as eluent. The yield of this reaction is 152 mg 61%.

후처리

  1. stirringThe solution was stirred for 1 h at 0° C. and 12 h at room temperature
  2. addition20 mL of Amberlite XAD-2 was added to the solution
  3. additionthe beads were thoroughly mixed with the solvent
  4. customthe THF evaporated off
  5. washThe beads were then washed with distilled water 6 times 100 mL
  6. extractionthen extracted three times with ethyl acetate (30 mL)
  7. customThe combined phase was evaporated
  8. customthe residue was dried under high vacuum
  9. customThe crude product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-2641b37a71ce4c7796375f08e23f4932
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08227450B2

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