Triethylamine → N-methoxy-N-methyl-(E)-3-{2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl}propenamide

HRID 1072289Notes

Reaction equation

HRID 1072289 reaction equation
[CH:1]1([C:4]2[C:13](/[CH:14]=[CH:15]/[C:16](O)=[O:17])=[C:12]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.Cl.[CH3:41][NH:42][O:43][CH3:44]>ClCCl>[CH:1]1([C:4]2[C:13](/[CH:14]=[CH:15]/[C:16]([N:42]([O:43][CH3:44])[CH3:41])=[O:17])=[C:12]([C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)2×HCID 22392019(E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-acrylic acid

Product 1

HCID 22392020N-methoxy-N-methyl-(E)-3-{2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl}propenamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (E)-3-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-acrylic acid (2.0 g, 6.0 mmol) in dichloromethane (25 ml) at −5° C. is added triethylamine (0.668 g, 6.6 mmol).and pivaloyl chloride (0.725 g, 6.0 mmol). After stirring at 0° C. for 170 min, N,O-dimethyl-hydroxylamine hydrochloride (0.59 g, 6.0 mmol) and triethylamine (1.22 g, 12.0 mmol) are added. After stirring in an ice bath for 90 min, and at room temperature for 30 min, more N,O-dimethylhydroxylamine hydrochloride (0.177 g, 1.8 mmol) is added and the reaction is stirred at room temperature for 17 h. After quenching with 0.2M citrate buffer pH5 (25 ml), the organic phase is separated and washed with 0.2M citrate buffer pH5 (25 ml), 0.2M phosphate buffer pH7 (25 ml) and water (25 ml). The water phases are extracted with dichloromethane (2×20 ml). Combined organic phases are dried over magnesium sulphate, evaporated, and the crude product chromatographed on silica gel (hexane/ethyl acetate 2:1) to afford (E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamide (7). MS (ES): [M+H]+ 377, Mp. 155-156° C.

Workup

  1. stirringAfter stirring in an ice bath for 90 min
  2. waitat room temperature for 30 min
  3. stirringthe reaction is stirred at room temperature for 17 h
  4. customAfter quenching with 0.2M citrate buffer pH5 (25 ml)
  5. customthe organic phase is separated
  6. washwashed with 0.2M citrate buffer pH5 (25 ml), 0.2M phosphate buffer pH7 (25 ml) and water (25 ml)
  7. extractionThe water phases are extracted with dichloromethane (2×20 ml)
  8. dry with materialCombined organic phases are dried over magnesium sulphate
  9. customevaporated
  10. customthe crude product chromatographed on silica gel (hexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-12aed8c883e74648a4066cd79a0451ca
Source dataset
uspto-grants-2005_06
Patent number
US06909003B2

Reaction notes

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