Diisopropylethylamine → Ombitasvir metabolite M6

HRID 1471059Notes

Reaction equation

HRID 1471059 reaction equation
[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]

Participants

6

Reactant 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

Product 1

HCID 49846541Ombitasvir metabolite M6Yield 48.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-0cab85afb8844dceb774a8dbf571c294
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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