4-Methylmorpholine → benzyl 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate

HRID 2045797Notes

Reaction equation

HRID 2045797 reaction equation
CN1CCOCC1.[CH:8]1([N:11]([C@H:19]2[C:28]3[CH:27]=[C:26]([F:29])[CH:25]=[CH:24][C:23]=3[N:22]([C:30](=[O:42])[C:31]3[CH:36]=[CH:35][C:34]([O:37][C:38]([F:41])([F:40])[F:39])=[CH:33][CH:32]=3)[C@H:21]3[CH2:43][CH2:44][CH2:45][C@@H:20]23)[C:12](=[O:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:10][CH2:9]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:70][CH:71]1[CH:76]([OH:77])[CH:75]([OH:78])[CH:74](O)[O:73][CH:72]1[C:80]([O:82][CH2:83][C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1)=[O:81]>C(#N)C.C(Cl)Cl.CO>[CH:8]1([N:11]([C@H:19]2[C:28]3[CH:27]=[C:26]([F:29])[CH:25]=[CH:24][C:23]=3[N:22]([C:30](=[O:42])[C:31]3[CH:32]=[CH:33][C:34]([O:37][C:38]([F:39])([F:41])[F:40])=[CH:35][CH:36]=3)[C@H:21]3[CH2:43][CH2:44][CH2:45][C@@H:20]23)[C:12](=[O:18])[CH2:13][CH2:14][C:15]([O:17][CH:74]2[O:73][CH:72]([C:80]([O:82][CH2:83][C:84]3[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=3)=[O:81])[CH:71]([OH:70])[CH:76]([OH:77])[CH:75]2[OH:78])=[O:16])[CH2:10][CH2:9]1

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 14602686benzyl 3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylateHCID 711185094-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid

Product 1

HCID 71140109benzyl 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylateYield 102.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

N-methylmorpholine (0.077 mL, 0.702 mmol) was added to a stirred mixture of 4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid (150 mg, 0.281 mmol), HATU (133 mg, 0.351 mmol) and benzyl 3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate (100 mg, 0.351 mmol) in acetonitrile (3 mL) and the mixture was stirred at room temperature for 3 h. TLC showed clean reaction (MeOH in DCM 10%). Solvent was removed and the residue was purified by column chromatography on silica gel (24 g prepacked column) eluting with DCM/MeOH gradient up to 20% MeOH to give benzyl 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate 174A (0.23 g).

Workup

  1. customSolvent was removed
  2. customthe residue was purified by column chromatography on silica gel (24 g prepacked column)
  3. washeluting with DCM/MeOH

Sources & evidence

ORD record
ord-7544fe7313c54d64b381aa218be82e53
Source dataset
uspto-grants-2013_11
Patent number
US08592383B2

Reaction notes

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