Diisopropylethylamine → HCID 178495662, compound

HRID 1751635Notes

Reaction equation

HRID 1751635 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][NH:7][C@H:6]([C:9]2[NH:13][C:12]3[C:14]4[C:19]([CH:20]=[CH:21][C:11]=3[N:10]=2)=[CH:18][C:17]2[C:22]3[C:27]([CH2:28][O:29][C:16]=2[CH:15]=4)=[CH:26][C:25]([C:30]2[NH:34][C:33]([C@@H:35]4[CH2:39][C@H:38]([CH3:40])[CH2:37][N:36]4[C:41](=[O:51])[C@@H:42]([NH:46][C:47](=[O:50])[O:48][CH3:49])[CH:43]([CH3:45])[CH3:44])=[N:32][CH:31]=2)=[CH:24][CH:23]=3)[CH2:5]1.[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>[CH3:52][O:53][C:54]([NH:56][C@@H:57]([CH:61]([CH3:63])[CH3:62])[C:58]([N:7]1[CH2:8][C@@H:4]([CH2:3][O:2][CH3:1])[CH2:5][C@H:6]1[C:9]1[NH:13][C:12]2[C:14]3[C:19]([CH:20]=[CH:21][C:11]=2[N:10]=1)=[CH:18][C:17]1[C:22]2[C:27]([CH2:28][O:29][C:16]=1[CH:15]=3)=[CH:26][C:25]([C:30]1[NH:34][C:33]([C@@H:35]3[CH2:39][C@H:38]([CH3:40])[CH2:37][N:36]3[C:41](=[O:51])[C@@H:42]([NH:46][C:47](=[O:50])[O:48][CH3:49])[CH:43]([CH3:45])[CH3:44])=[N:32][CH:31]=1)=[CH:24][CH:23]=2)=[O:59])=[O:55]

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-9b08d19b4a30419ba98be9d585ffed7e
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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