Sodium Carbonate → 1-(5-Phenyl pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline

HRID 989197Notes

Reaction equation

HRID 989197 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([O:24][CH3:25])=[C:17]([C:20]([F:23])([F:22])[F:21])[CH:18]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[N:6][CH:7]=1.[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:26]1([C:2]2[CH:3]=[C:4]([NH:8][C:9]([N:11]3[C:19]4[C:14](=[CH:15][C:16]([O:24][CH3:25])=[C:17]([C:20]([F:23])([F:22])[F:21])[CH:18]=4)[CH2:13][CH2:12]3)=[O:10])[CH:5]=[N:6][CH:7]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 10573917HCID 10573917, compound

Product 1

HCID 108355371-(5-Phenyl pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indolineYield 67.7%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

A mixture of 1-(5-bromo-pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl-indoline (D14, 208 mg, 0.5 mmol), phenyl boronic acid (300 mg, 2.4 mmol), sodium carbonate (0.32 g, 3 mmol) and tetrakis (triphenylphosphine) palladium (0) (30 mg) in dimethoxyethane-water (5 ml-1 ml) was heated to reflux under argon for 10 h. The cooled reaction mixture was partitioned between ethyl acetate-half saturated brine. The organic extract was dried and evaporated affording a brown solid (0.14 g). Chromatography on silica, eluting with a gradient of 0-5% methanol in ethyl acetate afforded the title compound as a white crystalline solid (100 mg, 48%), m.p. 162-164° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under argon for 10 h
  3. customThe cooled reaction mixture
  4. customwas partitioned between ethyl acetate-half saturated brine
  5. extractionThe organic extract
  6. customwas dried
  7. customevaporated

Sources & evidence

ORD record
ord-89752504e5b34a01b526e8f24d28bc88
Source dataset
uspto-grants-2003_10
Patent number
US06638953B2

Reaction notes

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