Methanol → HCID 87158984, compound

HRID 1844069Notes

Reaction equation

HRID 1844069 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:11][C:12]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][N:18]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][C:28]=3[CH3:29])[C:19]2=[O:22])=[CH:14][C:13]=1[OH:30].C1(N[S:38]([C:41]([F:44])([F:43])[F:42])(=[O:40])=[O:39])C=CC=CC=1.CO>C1COCC1.C(Cl)(Cl)Cl>[F:42][C:41]([F:44])([F:43])[S:38]([O:30][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:12]=1[Cl:11])[C:19](=[O:22])[N:18]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[CH3:29])[CH2:17][CH2:16]2)(=[O:40])=[O:39]

Participants

7

Reactant 4

HCID 887MethanolHCID 680121,1,1-Trifluoro-N-phenylmethanesulfonamideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66801965HCID 66801965, compound

Product 1

HCID 87158984HCID 87158984, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

KHMDS (0.23 mL (0.91M), 0.21 mmol) was added to a solution of 7-chloro-6-hydroxy-2-(4-methylpyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one (87A: 50 mg, 0.1736 mmol) in THF (5 mL) at −78° C. and stirred at −10° C. for 20 minutes, then cooled to −78° C., followed by the addition of N-phenyl trifluoromethanesulfonamide (68.2 mg, 0.190 mmol). The resulting mixture was stirred at room temperature for 60 minutes. The reaction was monitored by TLC (5% methanol in CHCl3). The reaction mixture was quenched with saturated NH4Cl solution and partitioned between water and 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) afforded 50 mg of the product (70% yield).

Workup

  1. temperaturecooled to −78° C.
  2. stirringThe resulting mixture was stirred at room temperature for 60 minutes
  3. customThe reaction mixture was quenched with saturated NH4Cl solution
  4. custompartitioned between water and ethyl acetate
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto afford the crude product
  8. customPurification by column chromatography on silica gel (2% methanol in CHCl3)

Sources & evidence

ORD record
ord-099e66ec77b9479ab4282ec28e9905ca
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

Loading…