Methyl iodide → HCID 58929005, compound

HRID 853648Notes

Reaction equation

HRID 853648 reaction equation
[CH:1]([O:14][C:15]1[C:16]2[C:35](=[O:36])[N:34]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:33][C:17]=2[C:18](OS(C(F)(F)F)(=O)=O)=[C:19]2[C:24]=1[N:23]=[CH:22][CH:21]=[CH:20]2)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:45]1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CI.[C:76]([O-:79])([O-])=[O:77].[Cs+].[Cs+]>CN(C=O)C.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:45][O:79][C:76]([C:18]1[C:19]2[CH:20]=[CH:21][CH:22]=[N:23][C:24]=2[C:15]([O:14][CH:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:16]2[C:35](=[O:36])[N:34]([CH2:37][C:38]3[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=3)[CH2:33][C:17]=12)=[O:77]

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 58928818HCID 58928818, compound

Product 1

HCID 58929005HCID 58929005, compoundYield 70%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To trifluoro-methanesulfonic acid 9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester 46 (1.48 g, 2.39 mmol) and 1,3-bis(diphenylphosphino)propane (DPPP) (295 mg, 0.7 mmol) in DMF (20 mL) and water (1 mL) in a two-necked round bottom flask were added Pd(OAc)2 (107 mg, 0.48 mmol). The solution was degassed under high vacuum and flushed with carbon monoxide from a balloon. The flushing was repeated five times. TEA (0.733 mL, 3.26 mmol) was introduced. The mixture was heated under CO atmosphere for 2.5 hours and cooled down to the room temperature. MeI (0.74 mL, 12 mmol) and Cs2CO3 were added and stirring was continued under a nitrogen atmosphere for 45 minutes. The mixture was diluted with EtOAc (300 mL), washed with water, 1N aqueous HCl and brine, dried over MgSO4 and concentrated. The crude product was purified by chromatography on a silica gel column eluting with 15% to 35% of EtOAc in hexane to afford 9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinoline-5-carboxylic acid methyl ester 212, (0.9 g, 1.69 mmol, 70%) as a yellow solid. 1H NMR (CDCl3): 89.25 (d, 1H), 9.05 (m, 1H), 7.80 (d, 4H), 7.56 (dd, 1H), 7.0-7.4 (m, 11H), 4.85 (s, 2H), 4.55 (s, 2H), 3.95 (s, 3H); MS: 555 (M+Na).

Workup

  1. customThe solution was degassed under high vacuum
  2. customflushed with carbon monoxide from a balloon
  3. temperatureThe mixture was heated under CO atmosphere for 2.5 hours
  4. washwashed with water, 1N aqueous HCl and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography on a silica gel column
  8. washeluting with 15% to 35% of EtOAc in hexane

Sources & evidence

ORD record
ord-f46e6abdb0d44bfca51b69844906810f
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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