Diisopropylethylamine → HCID 57639109, 화합물

HRID 2111948노트

반응식

HRID 2111948 반응식
[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

참가 물질

8

반응물 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-dimethylpiperazine2회HCID 59682115HCID 59682115, 화합물

생성물 1

HCID 57639109HCID 57639109, 화합물수율 14.1%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b7386e5524ea407aba6d805564eebcb5
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07521441B2

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