Diisopropylethylamine → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

HRID 85608노트

반응식

HRID 85608 반응식
[NH2:1][C@:2]12[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:34])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:74]([O:78][C:79]([NH:81][C:82]1([C:85](O)=[O:86])[CH2:84][CH2:83]1)=[O:80])([CH3:77])([CH3:76])[CH3:75]>C(Cl)Cl>[C:74]([O:78][C:79]([NH:81][C:82]1([C:85]([NH:1][C@:2]23[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]2[C@@H:4]2[C@@:17]([CH3:20])([CH2:18][CH2:19]3)[C@@:16]3([CH3:21])[C@@H:7]([C@:8]4([CH3:34])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:22])([CH3:23])[C:11]([C:24]3[CH:25]=[CH:26][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=3)=[CH:10][CH2:9]4)[CH2:6][CH2:5]2)=[O:86])[CH2:84][CH2:83]1)=[O:80])([CH3:77])([CH3:76])[CH3:75]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68357865methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

생성물 1

HCID 68357872methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate수율 55.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (0.302 g, 0.555 mmol) and N,N-diisopropylethylamine (0.580 mL, 3.33 mmol) in DCM (5 mL) was added 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.465 g, 1.222 mmol) and 1-(tert-butoxycarbonylamino)cyclopropanecarboxylic acid (0.223 g, 1.111 mmol). The reaction mixture was stirred at rt. After 18 h, the reaction was diluted with DCM (20 mL) and silica gel (4 g) was added. The mixture was concentrated to dryness and dried in vacuo to a free flowing powder. The material was loaded onto a silica gel column (25 g cartridge) gradient 100% hexanes to 25% EtOAc in hexanes over 240 mL, hold 25% EtOAc in hexanes to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (234 mg, 0.309 mmol, 55.6% yield) as a white solid. LCMS: m/e 727.4 (M+H)+, 5.17 min (method 2). 1H NMR (500 MHz, CHLOROFORM-d) δ 7.97-7.89 (m, 2H), 7.20 (d, J=8.5 Hz, 2H), 6.47 (br. s., 1H), 5.30 (dd, J=6.3, 1.7 Hz, 1H), 5.16-5.06 (m, 1H), 4.72 (d, J=1.8 Hz, 1H), 4.62 (s, 1H), 4.19-4.09 (m, 1H), 3.92 (s, 3H), 2.66-2.60 (m, 1H), 2.49 (d, J=4.6 Hz, 2H), 2.11 (dd, J=17.1, 6.4 Hz, 1H), 2.07-1.96 (m, 1H), 1.53 (s, 9H), 1.46 (s, 3H), 1.43 (d, J=2.7 Hz, 1H), 1.37 (d, J=3.4 Hz, 1H), 1.34 (d, J=3.7 Hz, 1H), 1.26 (dd, J=7.0, 3.1 Hz, 1H), 1.19-1.16 (m, 1H), 1.12 (br. s., 3H), 1.10-1.07 (m, 1H), 1.01 (s, 3H), 1.01-0.99 (m, 3H), 0.94 (s, 3H), 0.94 (s, 3H).

후처리

  1. additionwas added
  2. concentrationThe mixture was concentrated to dryness
  3. customdried in vacuo to

출처 및 근거

ORD 기록
ord-bbadf8e34a7249b18de794f9602a4413
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846647B2

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