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

HRID 446976ノート

反応式

HRID 446976 の反応式
[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

参加物

7

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-f671432fd3064f73bbaa767f8db0d5d4
出典データセット
uspto-grants-2013_07
特許番号
US08481495B2

反応ノート

読み込み中…