Diisopropylethylamine → HCID 178495662, compound

HRID 1412940Notes

Reaction equation

HRID 1412940 reaction equation
[CH3:1][O:2][C:3](=[O:51])[NH:4][C@@H:5]([CH:48]([CH3:50])[CH3:49])[C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[C:23]3[CH2:25][O:26][C:27]4[CH:47]=[C:46]5[C:30]([CH:31]=[CH:32][C:33]6[N:37]=[C:36]([C@@H:38]7[CH2:42][C@H:41]([CH2:43][O:44][CH3:45])[CH2:40][NH:39]7)[NH:35][C:34]=65)=[CH:29][C:28]=4[C:22]3=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=[O:7].[CH3:52][O:53][C:54]([NH:56][CH:57]([CH:61]([CH3:63])[CH3:62])[C:58](O)=[O:59])=[O:55].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:51])[NH:4][C@@H:5]([CH:48]([CH3:50])[CH3:49])[C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[C:23]3[CH2:25][O:26][C:27]4[CH:47]=[C:46]5[C:30]([CH:31]=[CH:32][C:33]6[N:37]=[C:36]([C@@H:38]7[CH2:42][C@H:41]([CH2:43][O:44][CH3:45])[CH2:40][N:39]7[C:58](=[O:59])[C@@H:57]([NH:56][C:54]([O:53][CH3:52])=[O:55])[CH:61]([CH3:63])[CH3:62])[NH:35][C:34]=65)=[CH:29][C:28]=4[C:22]3=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=[O:7]

Participants

7

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 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178495705HCID 178495705, compound

Product 1

HCID 178495662HCID 178495662, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl{(2S)-1-[(2S,4S)-2-(5-{2-[(2S,4S)-4-(methoxymethyl)pyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-4-(methyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (57 mg, 0.08 mmol), 2-methoxycarbonylamino-3-methylbutyric acid (19 mg, 0.1 mmol), HATU (303 mg, 0.79 mmol) in DMF (1 mL) was added diisopropylethylamine (43 μL, 0.24 mmol). After stirring for 2 hours at room temperature, the reaction was diluted with ethyl acetate, washed with 5% NaHCO3 solution, water and brine, dried (Na2SO4), concentrated and purified by preparative reverse phase HPLC (Gemini, 15 to 43% ACN/H2O+0.1% TFA). The product fractions were lyophilized to give methyl{(2S)-1-[(2S,4S)-2-(5-{2-[(2S,4S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methyl butanoyl}-4-methoxymethylpyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate. (13 mg, 19%). MS (ESI) m/z 850 [M+H]+.

Workup

  1. washwashed with 5% NaHCO3 solution, water and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. custompurified by preparative reverse phase HPLC (Gemini, 15 to 43% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-a854e176a3c946f2a610bfbd92a0a292
Source dataset
uspto-grants-2014_12
Patent number
US08921341B2

Reaction notes

Loading…