Diisopropyl Ether → HCID 68671831, compound

HRID 2192941Notes

Reaction equation

HRID 2192941 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[C:17](O)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.C(Cl)(=O)C([Cl:30])=O.[CH3:33][C:34]1[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=1.C(OC(C)C)(C)C>ClCCl.CN(C=O)C.N1C=CC=CC=1.O>[ClH:30].[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:26][CH2:25][C:23](=[O:24])[CH2:22]3)[C:17]([NH:40][C:37]3[CH:36]=[CH:35][C:34]([CH3:33])=[CH:39][N:38]=3)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 7914Diisopropyl EtherHCID 153482-Amino-5-methylpyridineHCID 65578Oxalyl chlorideHCID 59570915HCID 59570915, compound

Product 1

HCID 68671831HCID 68671831, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propionic acid (200 mg) in dichloromethane (5 mL) was added sequentially a solution of oxalyl chloride in 1 M dichloromethane (0.64 mL) and DMF (16 μL), followed by stirring for 1 hour under ice-cooling. Thereafter, a solution of 5-methylpyridin-2-amine (63 mg) in dichloromethane (5 mL) and pyridine (0.09 mL) were added thereto under ice-cooling, followed by stirring for 2 hours under ice-cooling. To the reaction mixture was added water under ice-cooling, followed by extraction with ethyl acetate. The organic layer was sequentially washed with a 5% aqueous citric acid solution, saturated aqueous sodium bicarbonate, and saturated brine, and dried over anhydrous magnesium sulfate. The oily substance obtained by concentration was purified by silica gel column chromatography (wetting with hexane:ethyl acetate=1:1, chloroform:methanol=1:0-10:1). The obtained oily substance was dissolved in ethyl acetate (4 mL), and 4 M hydrogen chloride/ethyl acetate (1 mL) was added thereto, followed by stirring at room temperature for 30 minutes. The oily substance obtained by concentration was solidified with diisopropyl ether and collected by filtration to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyridin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide monohydrochloride (210 mg) as a white solid.

Workup

  1. temperaturecooling
  2. temperatureunder ice-cooling
  3. stirringby stirring for 2 hours under ice-
  4. temperaturecooling
  5. temperaturecooling
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was sequentially washed with a 5% aqueous citric acid solution, saturated aqueous sodium bicarbonate, and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe oily substance obtained by concentration
  10. customwas purified by silica gel column chromatography (wetting with hexane:ethyl acetate=1:1, chloroform:methanol=1:0-10:1)
  11. dissolutionThe obtained oily substance was dissolved in ethyl acetate (4 mL)
  12. addition4 M hydrogen chloride/ethyl acetate (1 mL) was added
  13. stirringby stirring at room temperature for 30 minutes
  14. customThe oily substance obtained by concentration
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-51f7dfa259fe4fdf90a7ad836edc9abf
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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