3,4-Dimethoxyphenylboronic acid → HCID 49835026, compound

HRID 445544Notes

Reaction equation

HRID 445544 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[CH:16]=[N:17][N:18]([CH3:21])[C:19]=4[CH3:20])[C:5]=3[C:4]=2[CH:3]=1.[CH3:24][O:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33]>CN(C=O)C.C([O-])([O-])=O.[K+].[K+].CO.CC(N(C)C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:24][O:25][C:26]1[CH:27]=[C:28]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]5[CH:16]=[N:17][N:18]([CH3:21])[C:19]=5[CH3:20])[C:5]=4[C:4]=3[CH:3]=2)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33]

Participants

7

Reactant 2

HCID 27347023,4-Dimethoxyphenylboronic acidHCID 596196828-bromo-1-(1,5-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one2×

Product 1

HCID 49835026HCID 49835026, compound

Reagents, catalysts & solvents 4

HCID 17933507HCID 17933507, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 8-bromo-1-(1,5-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Intermediate J, 50 mg, 0.132 mmol), 3,4-dimethoxyphenylboronic acid (Aldrich, Buchs, Switzerland, 29 mg, 0.156 mmol) and PdCl2(PPh3)2 (6 mg, 0.0085 mmol) in DMF (1.2 ml) and 1 M aqueous K2CO3 (0.329 ml) was stirred under argon at 105° C. for 1.5 h. Then the RM was cooled to rt, diluted with MeOH/DMA+3 drops TFA and purified directly by Prep. HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 55:45). The fractions containing product were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting suspension was filtered and the cake was washed with water, before being dried under high vacuum to give the title compound as an off-white solid. (HPLC: tR 2.66 min (Method A); M+H=430 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.92 (s, 1H), 8.08-8.01 (m, 1H), 7.95-7.88 (m, 1H), 7.76 (s, 1H), 7.60-7.55 (m, 1H), 7.13-7.08 (m, 1H), 7.05-7.00 (m, 1H), 6.99-6.94 (m, 1H), 3.88-382 (m, 6H), 3.78 (s, 3H), 3.56 (s, 3H), 2.11 (s, 3H))

Workup

  1. temperatureThen the RM was cooled to rt
  2. custompurified directly by Prep
  3. additionThe fractions containing product
  4. customwere collected together
  5. concentrationbefore being concentrated
  6. filtrationThe resulting suspension was filtered
  7. washthe cake was washed with water
  8. custombefore being dried under high vacuum

Sources & evidence

ORD record
ord-c16811ef65f04a158e37a2ba599f7680
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

Loading…