Methanol → N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide

HRID 1014893노트

반응식

HRID 1014893 반응식
[Si](O[C@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)[C@@H:10]([NH:20][C:21](=[O:38])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([N:30]2[CH2:34][CH2:33][CH2:32][C@@H:31]2[CH2:35]OC)=[O:29])[CH:23]=1)[CH2:11]C1C=C(F)C=C(F)C=1)(C(C)(C)C)(C)C.C(OC([C@@H:65]([CH2:93][C:94]1[CH:99]=[CH:98][CH:97]=[CH:96][CH:95]=1)[C@@H:66]([C@H:75]1[CH2:79][C@@H:78]([S:80]([CH2:83][CH2:84][CH3:85])(=[O:82])=[O:81])[CH2:77][N:76]1C(OC(C)(C)C)=O)[O:67][Si](C(C)(C)C)(C)C)=O)C1C=CC=CC=1.C([O:104][C:105]([N:107]1C[C@H](OCCC)C[C@@H]1[C@@H](O[Si](C(C)(C)C)(C)C)[C@@H](NC(C1C=C(C=CC=1)C(O)=O)=O)CC1C=C(F)C=C(F)C=1)=O)(C)(C)C.OOS([O-])=O.[K+].[CH3:153]O>O>[OH:67][C@H:66]([C@H:75]1[CH2:79][C@@H:78]([S:80]([CH2:83][CH2:84][CH3:85])(=[O:81])=[O:82])[CH2:77][NH:76]1)[C@@H:65]([NH:107][C:105](=[O:104])[C:26]1[CH:27]=[C:22]([C:21]2[O:38][CH:11]=[CH:10][N:20]=2)[CH:23]=[C:24]([C:28]([N:30]([CH2:31][CH2:35][CH3:153])[CH2:34][CH2:33][CH3:32])=[O:29])[CH:25]=1)[CH2:93][C:94]1[CH:95]=[CH:96][CH:97]=[CH:98][CH:99]=1

참가 물질

7

반응물 5

HCID 887MethanolHCID 23707502Potassium hydroxy sulfiteHCID 67315894(2r,4r)-Tert-butyl 2-((1s,2s)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylateHCID 673161403-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acidHCID 67316242(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

생성물 1

HCID 11848640N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide수율 64%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

Step 17 (D): (2R,4R)-tert-butyl 2-((1S,2S)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate. A solution of 130 mg (0.2 mmol) of the compound of step 17 (C) dissolved in 2 mL of methanol was treated with a solution of 240 mg (0.4 mmol) of oxone dissolved in 0.4 mL of water. After stirring at rt for 30 min, the reaction solution was partitioned between ethyl acetate and water, the organic layer was concentrated, and the crude product was purified by chromatography eluting with a gradient of 20 to 80% ethyl acetate in hexanes to provide 86 mg (64%) of the desired sulfone and 37 mg (28%) of the sulfoxide intermediate as a lower-eluting compound. 1H NMR (500 MHz, CDCl3) δ ppm 0.06 (s, 3 H) 0.11 (s, 3 H) 0.96 (s, 9 H) 1.07 (t, J=7.32 Hz, 3 H) 1.47 (s, 9 H) 1.87 (dd, J=13.43, 6.71 Hz, 3 H) 2.03 (s, 1 H) 2.26 (t, J=12.21 Hz, 1 H) 2.38 (s, 1 H) 2.68 (s, 1 H) 2.90 (s, 2 H) 3.46 (m, 2 H) 3.75 (s, 1 H) 4.09 (m, 2 H) 4.26 (d, J=7.02 Hz, 1 H) 4.77 (m, 1 H) 4.95 (m, 1 H) 7.18 (m, 10 H) MS (ESI) (M+H-Boc)+=575.25

후처리

  1. customthe reaction solution was partitioned between ethyl acetate and water
  2. concentrationthe organic layer was concentrated
  3. customthe crude product was purified by chromatography
  4. washeluting with a gradient of 20 to 80% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-6af53e5ace9040a08ec4dea3aa00c1ca
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981913B2

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