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 85608

反応式

HRID 85608 の反応式
[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]

参加物

6

反応物 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

生成物 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)benzoate収率 55.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-bbadf8e34a7249b18de794f9602a4413
出典データセット
uspto-grants-2014_09
特許番号
US08846647B2

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