4-Methylmorpholine → HCID 178495684, compound

HRID 1413019Notes

Reaction equation

HRID 1413019 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[C@@H:16]([CH3:17])[CH2:15][CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[C:23]3[C:28]([CH:29]=[CH:30][C:20]=2[N:19]=1)=[CH:27][C:26]1[C:31]2[C:36]([CH2:37][O:38][C:25]=1[CH:24]=3)=[CH:35][C:34]([C:39]1[NH:43][C:42]([C@@H:44]3[CH2:48][C@H:47]([CH2:49][O:50][CH3:51])[CH2:46][N:45]3[C:52](OC(C)(C)C)=[O:53])=[N:41][CH:40]=1)=[CH:33][CH:32]=2)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].[CH3:59][O:60][C:61]([NH:63][C@@H:64]([CH:68]([CH3:70])[CH3:69])C(O)=O)=[O:62].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>Cl.CCO.CN(C=O)C>[CH3:1][O:2][C:3](=[O:4])[NH:5][C@@H:6]([CH:7]([CH3:8])[CH3:9])[C:10]([N:12]1[C@@H:16]([CH3:17])[CH2:15][CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[C:23]3[C:28]([CH:29]=[CH:30][C:20]=2[N:19]=1)=[CH:27][C:26]1[C:31]2[C:36]([CH2:37][O:38][C:25]=1[CH:24]=3)=[CH:35][C:34]([C:39]1[NH:43][C:42]([C@@H:44]3[CH2:48][C@H:47]([CH2:49][O:50][CH3:51])[CH2:46][N:45]3[C:52](=[O:53])[C@@H:64]([NH:63][C:61]([O:60][CH3:59])=[O:62])[CH:68]([CH3:70])[CH3:69])=[N:41][CH:40]=1)=[CH:33][CH:32]=2)=[O:11]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 1784956861-Pyrrolidinecarboxylic acid, 2-[5-[1,11-dihydro-2-[(2S,5S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methyl-1-oxobutyl]-5-methyl-2-pyrrolidinyl][2]benzopyrano[4',3':6,7]naphth[1,2-d]imidazol-9-yl]-1H-imidazol-2-yl]-4-(methoxymethyl)-, 1,1-dimethylethyl ester, (2S,4S)-

Product 1

HCID 178495684HCID 178495684, compoundYield 82.5%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

Tert-butyl(2S,4S)-2-[5-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (100 mg, 0.13 mmol) in 1.25 N HCl in EtOH (3 mL) was heated to 50° C. for 3 h and then concentrated under reduced pressure. The crude residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (34 mg, 0.20 mmol), HATU (54 mg, 0.14 mmol) and DMF (1.3 mL), then N-methylmorpholine (0.043 mL, 0.39 mmol) was added dropwise. After 3 h, the mixture was quenched with 1N HCl (0.100 mL) and then purified by HPLC to afford methyl{(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (91 mg, 82%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customthe mixture was quenched with 1N HCl (0.100 mL)
  3. custompurified by HPLC

Sources & evidence

ORD record
ord-aee7686be0f442b1b91bea274a25306f
Source dataset
uspto-grants-2014_12
Patent number
US08921341B2

Reaction notes

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