Diisopropylethylamine → Ombitasvir metabolite M6

HRID 1471059노트

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HRID 1471059 반응식
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:17]([CH3:19])[CH3:18])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([OH:16])=O)=[O:8])=[O:4].[C:20]([C:24]1[CH:29]=[CH:28][C:27]([N:30]2[C@H:34]([C:35]3[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=3)[CH2:33][CH2:32][C@H:31]2[C:42]2[CH:48]=[CH:47][C:45]([NH2:46])=[CH:44][CH:43]=2)=[CH:26][CH:25]=1)([CH3:23])([CH3:22])[CH3:21].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>CS(C)=O>[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([NH:39][C:38]1[CH:37]=[CH:36][C:35]([C@@H:34]2[CH2:33][CH2:32][C@@H:31]([C:42]3[CH:48]=[CH:47][C:45]([NH2:46])=[CH:44][CH:43]=3)[N:30]2[C:27]2[CH:26]=[CH:25][C:24]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:29][CH:28]=2)=[CH:41][CH:40]=1)=[O:16])=[O:8])[CH:17]([CH3:19])[CH3:18])=[O:4]

참가 물질

6

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 12071044(S)-1-((S)-2-((Methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acidHCID 67239053A-1242846

생성물 1

HCID 49846541Ombitasvir metabolite M6수율 48.1%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

To a solution of the product from Example 37B (17.7 mg, 0.065 mmol) and the product from Example 37E (50 mg, 0.130 mmol) in anhydrous DMSO (1.3 mL) was added HATU (27.1 mg, 0.071 mmol) and Hunig's Base (0.015 mL, 0.084 mmol). The resulting mixture was stirred at rt for 30 min, and was then partitioned between H2O (5 mL) and EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4. The drying agent was filtered off, and solvent was removed in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% MeOH in CH2Cl2 to give the title compound (20 mg, 24%). 1H NMR (400 MHz, DMSO-D6) δ ppm 0.88 (d, J=6.72 Hz, 3H), 0.93 (d, J=6.72 Hz, 3H), 1.11 (s, 9H), 1.52-1.66 (m, 2H), 1.79-2.06 (m, 4H), 2.06-2.20 (m, 1H), 2.34-2.47 (m, 2H), 3.52 (s, 3H), 3.56-3.67 (m, 1H), 3.74-3.87 (m, 1H), 4.02 (t, J=8.51 Hz, 1H), 4.42 (dd, J=8.08, 4.83 Hz, 1H), 4.83-4.94 (m, 2H), 5.02 (d, J=7.16 Hz, 0.5H), 5.08 (d, 7.59 Hz, 0.5H), 6.18 (d, 8.78 Hz, 2H), 6.48 (d, J=8.35 Hz, 2H), 6.84 (d, J=8.35 Hz, 2H), 6.93 (d, J=8.89 Hz, 2H), 7.11 (d, J=8.57 Hz, 2H), 7.31 (d, J=8.35 Hz, 1H), 7.48 (d, J=8.57 Hz, 2H), 9.97 (s, 1H); MS (ESI) m/z 640.3 (M+H)+.

후처리

  1. customwas then partitioned between H2O (5 mL) and EtOAc (3×5 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationThe drying agent was filtered off
  4. customsolvent was removed in vacuo
  5. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% MeOH in CH2Cl2

출처 및 근거

ORD 기록
ord-0cab85afb8844dceb774a8dbf571c294
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006387B2

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