Dichloromethane → HCID 86613794, compound

HRID 2378112Notes

Reaction equation

HRID 2378112 reaction equation
ClCCl.[CH:4]([O:7][C:8]([N:10]1[C:19]2[C:14](=[N:15][C:16](Br)=[CH:17][CH:18]=2)[C@H:13]([N:21]([C:37](=[O:39])[CH3:38])[CH2:22][C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=2)[CH2:12][C@@H:11]1[CH2:40][CH3:41])=[O:9])([CH3:6])[CH3:5].[CH3:42]B(O)O.[F-].[Cs+]>O1CCOCC1.O>[CH:4]([O:7][C:8]([N:10]1[C:19]2[C:14](=[N:15][C:16]([CH3:42])=[CH:17][CH:18]=2)[C@H:13]([N:21]([C:37](=[O:39])[CH3:38])[CH2:22][C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=2)[CH2:12][C@@H:11]1[CH2:40][CH3:41])=[O:9])([CH3:6])[CH3:5]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 86613793HCID 86613793, compound

Product 1

HCID 86613794HCID 86613794, compoundYield 84.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Add 1,1′-bis(diphenylphosphino)(II) chloride, complex with dichloromethane (9 mg, 0.012 mmol) to a suspension of (+/−)-cis-4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-bromo-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid isopropyl ester (50 mg, 0.08 mmol), methyl boronic acid (15 mg, 0.24 mmol) and cesium fluoride (40 mg, 0.28 mmol) in dry dioxane (1.5 mL) and heat the mixture at 80° C. in a sealed tube for 15 h. Cool the reaction mixture to room temperature, add water and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Chromatograph the residue over a silica gel cartridge, eluting with hexanes/ethyl acetate to provide the title compound (37 mg, 84%). MS (ES+): 546 (M+H).

Workup

  1. temperatureCool the reaction mixture to room temperature
  2. extractionextract with dichloromethane
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. washChromatograph the residue over a silica gel cartridge, eluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-9db07c1c2c9349b9b6efb184ec4d9c11
Source dataset
uspto-grants-2008_12
Patent number
US07470705B2

Reaction notes

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