Methanol → HCID 56940828, compound

HRID 1844070Notes

Reaction equation

HRID 1844070 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[Cl:17])[C:13](=[O:18])[N:12]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[CH3:25])[CH2:11][CH2:10]2)(=O)=O.CO.C([O-])([O-])=O.[Na+].[Na+].[CH3:36][N:37](C=O)C>C(Cl)(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2]>[Cl:17][C:16]1[CH:15]=[C:14]2[C:9]([CH2:10][CH2:11][N:12]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][C:24]=3[CH3:25])[C:13]2=[O:18])=[CH:8][C:7]=1[C:36]#[N:37]

Participants

9

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 87158984HCID 87158984, compound

Product 1

HCID 56940828HCID 56940828, compoundYield 10.6%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3 (17.4 mg, 0.018 mmol), dppf (42.2 mg, 0.076 mmol) and Zn(CN)2 (65 mg, 0.6 mmol) were added to previously degassed 7-chloro-2-(4-methylpyridin-3-yl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl trifluoromethane sulfonate (I-87a: 200 mg, 0.476 mmol) in DMF (3 mL). The resulting mixture was stirred for 18 hours at 80° C. The reaction was monitored by TLC (5% methanol in CHCl3). The reaction mixture was cooled to room temperature, poured into saturated Na2CO3 solution and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3), followed by preparative HPLC afforded 5 mg of the product (10.6% yield).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product
  6. customPurification by column chromatography on silica gel (2% methanol in CHCl3)

Sources & evidence

ORD record
ord-c8fb1a7d14684e5e84ca692cf3770839
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

Loading…