Diisopropylethylamine → HCID 57639109、化合物

HRID 2111948ノート

反応式

HRID 2111948 の反応式
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:30](=[O:38])[NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21](O)=[O:22])=[CH:18][C:17]4[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:39]([N:46]1[CH2:51][C@H:50]([CH3:52])[NH:49][C@H:48]([CH3:53])[CH2:47]1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.Cl>[CH2:39]([N:46]1[CH2:47][C@H:48]([CH3:53])[N:49]([C:21]([C:19]2[CH2:20][N:14]3[C:13]4[CH:12]=[C:11]([C:30]([NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[O:38])[CH:10]=[CH:9][C:8]=4[C:7]([CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[C:15]3[C:16]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:17]=3[CH:18]=2)=[O:22])[C@H:50]([CH3:52])[CH2:51]1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12197174(3r,5s)-1-Benzyl-3,5-dimethylpiperazine2 回HCID 59682115HCID 59682115、化合物

生成物 1

HCID 57639109HCID 57639109、化合物収率 14.1%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of 13-cyclohexyl-10-(((dimethylamino)sulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (200 mg, 0.37 mmol), (3R,5S)-1-benzyl-3,5-dimethylpiperazine (115 mg, 0.56 mmol) and diisopropylethylamine (0.26 mL) in DMF (4 mL) was added HATU (212 mg, 0.56 mmol). The reaction mixture was stirred at rt for 2 h, treated with additional (3R,5S)-1-benzyl-3,5-dimethylpiperazine (100 mg, 0.49 mmol) and stirred at 100° C. for 3 h. The reaction was cooled to rt, diluted with H2O (30 mL) and 1M HCl (aq.) (1.5 mL) and extracted with EtOAc (20 mL). The organic layer was separated, washed with brine (10 mL), dried (MsSO4), filtered and concentrated. The residue was diluted with MeOH (5 mL) and purified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc buffer) to yield rel-6-(((2R,6S)-4-benzyl-2,6-dimethyl-1-piperazinyl)carbonyl)-13-cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (38 mg, 0.052 mmol, 14%) as an orange solid. 1HNMR (300 MHz, CD3OD) δ 1.02-2.22 (m, 20H), 2.58-3.03 (m, 3H), 3.05 (s, 6H), 3.27-3.40 (m, 2H), 3.92 (s, 3H), 4.34-4.56 (m, 1H), 4.99-5.19 (m, 1H), 6.89 (s, 1H) 7.08 (d, J=2.6 Hz, 1H), 7.14 (dd, J=8.8, 2.6 Hz, 1H), 7.19-7.33 (m, 5H), 7.55 (d, J=8.4 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.90 (d, J=8.4 Hz, 1H), 8.17 (s, 1H). LCMS: m/e 724 (M+H)+, ret time 3.37 min, column B, 4 minute gradient.

後処理

  1. stirringstirred at 100° C. for 3 h
  2. temperatureThe reaction was cooled to rt
  3. extractionextracted with EtOAc (20 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. customdried (MsSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionThe residue was diluted with MeOH (5 mL)
  10. custompurified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc buffer)

出典と根拠

ORDレコード
ord-b7386e5524ea407aba6d805564eebcb5
出典データセット
uspto-grants-2009_04
特許番号
US07521441B2

反応ノート

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