Diisopropylethylamine → 4-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

HRID 446976노트

반응식

HRID 446976 반응식
[NH:1]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C@H:2]([C:9]([OH:11])=O)[CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:52]([O:59][C:60]([N:62]1[CH2:66][CH:65]([C:67](=[O:75])[NH:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH:64]2[NH:76][CH2:77][CH2:78][CH:63]12)=[O:61])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN1C(=O)CCC1.CCOCC>[CH2:52]([O:59][C:60]([N:62]1[CH2:66][CH:65]([C:67](=[O:75])[NH:68][C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[CH:64]2[N:76]([C:9](=[O:11])[CH:2]([NH:1][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:3]3[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]3)[CH2:77][CH2:78][CH:63]12)=[O:61])[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67281286HCID 67281286, 화합물

생성물 1

HCID 672814864-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester수율 92.8%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of Boc-Chg-OH (222 mg, 0.86 mmol) in NMP (5 mL) was cooled to 0° C. and treated with HATU (328 mg, 0.86 mmol) and DIPEA (0.17 mL, 0.98 mmol) followed, in 15 min, by the addition of 38 (300 mg, 0.82 mmol). The reaction mixture was allowed to warm to ambient temperature. After 18 h, the solution was diluted with Et2O, washed with H2O, 1M HCl, H2O, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by column chromatograhpy on silica gel with 2:1 hexane:EtOAc afforded 39 (460 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), mixture of rotamers: δ9.96 (d, J=18.9 Hz, 0.5H), 7.68 (d, J=9 Hz, 1H), 7.61 (d, J=7.5 Hz, 1H), 7.39-7.28 (m, 7H), 7.10 (dd, J=7.2, 15 Hz, 1H), 5.32-5.28 (m, 0.5H), 5.20-5.12 (m, 2.5H), 4.81-4.78 (m, 0.5H), 4.70 (d, J=6.6 Hz, 0.5H), 4.55-4.49 (m, 1H), 4.39-4.27 (m, 1.5H), 4.02-3.99 (m, 1H), 3.54-3.40 (m, 2H), 3.22-3.09 (m, 2H), 2.51-2.26 (m, 1H), 2.10-2.09 (m, 0.5H), 1.94-1.62 (m, 8H), 1.52-1.43 (m, 11H), 1.18-0.86 (m, 6H) ppm. Mass spectrum, m/z [605.7] (M+H)+.

후처리

  1. washwashed with H2O, 1M HCl, H2O, saturated aqueous NaHCO3, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatograhpy on silica gel with 2:1 hexane

출처 및 근거

ORD 기록
ord-f671432fd3064f73bbaa767f8db0d5d4
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481495B2

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