Potassium Carbonate → N-cyclopropyl-3-(7-methoxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide

HRID 507003Notes

Reaction equation

HRID 507003 reaction equation
[CH2:1]([N:4]([C:16]1[CH:21]=[C:20]([C:22]([NH:24][CH:25]2[CH2:27][CH2:26]2)=[O:23])[CH:19]=[CH:18][C:17]=1[CH3:28])[C:5](=[O:15])[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=1Br)[CH:2]=[CH2:3].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CC)(CC)CC)C.CN(C=O)C.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:25]1([NH:24][C:22](=[O:23])[C:20]2[CH:19]=[CH:18][C:17]([CH3:28])=[C:16]([N:4]3[CH:1]=[C:2]([CH3:3])[C:7]4[C:6](=[CH:11][C:10]([O:12][CH3:13])=[CH:9][CH:8]=4)[C:5]3=[O:15])[CH:21]=2)[CH2:27][CH2:26]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 67018660N-allyl-2-bromo-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-methoxybenzamide

Product 1

HCID 11710269N-cyclopropyl-3-(7-methoxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamideYield 31.5%

Reagents, catalysts & solvents 4

HCID 6285Tetraethylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

N-allyl-2-bromo-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-methoxybenzamide (1.03 g), tri-o-tolylphosphine (283 mg), tetraethylammonium bromide (977 mg) and potassium carbonate (1.3 g) were suspended in DMF (36 ml) under argon. Pd(OAc)2 (104 mg) was added and the mixture was heated at 120° C. for 17 hours and then allowed to cool. The reaction mixture was diluted with ethyl acetate and washed with water (×5), brine, dried (magnesium sulfate) and concentrated. Purification by column chromatography on a silica column eluting using a gradient of 50% ethyl acetate/iso-hexane to 100% ethyl acetate/iso-hexane to yield N-cyclopropyl-3-(7-methoxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide as a pale yellow foam (265 mg); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.69 (m, 2H), 2.11 (s, 3H), 2.27 (s, 3H), 2.86 (m, 1H), 3.89 (s, 3H), 7.10 (s, 1H), 7.46-7.51 (m, 2H), 7.71-7.76 (m, 3H), 7.87 (d, 1H), 8.46 (d, 1H); Mass Spectrum: M+H+ 363.

Workup

  1. temperatureto cool
  2. washwashed with water (×5), brine
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated
  5. customPurification by column chromatography on a silica column
  6. washeluting

Sources & evidence

ORD record
ord-e44b1a987dde40efabf5ed114d52985d
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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