(6-Methoxypyridin-3-yl)boronic acid → HCID 59620052, compound

HRID 445674Notes

Reaction equation

HRID 445674 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12](C)[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][N:27]=1>CN(C=O)C.C([O-])([O-])=O.[K+].[K+].CO.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>[CH3:20][N:18]1[CH:19]=[C:15]([N:14]2[C:5]3[C:4]4[CH:3]=[C:2]([C:29]5[CH:28]=[N:27][C:26]([O:25][CH3:24])=[CH:31][CH:30]=5)[CH:11]=[CH:10][C:9]=4[N:8]=[CH:7][C:6]=3[NH:12][C:13]2=[O:22])[C:16]([CH3:21])=[N:17]1

Participants

7

Reactant 2

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 596197398-Bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 59620052HCID 59620052, compound

Reagents, catalysts & solvents 4

HCID 887MethanolCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 8-bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Stage A.1, 49 mg, 0.137 mmol), 2-methoxypyridine-5-boronic acid (Sigma-Aldrich, Buchs, Switzerland, 26 mg, 0.170 mmol), and PdCl2(PPh3)2 (6 mg, 0.0085 mmol) in DMF (1.2 ml) and 1 M aqueous K2CO3 (0.343 ml) was stirred under argon at 105° C. for 1.5 h. The RM was cooled toll. The mixture was diluted with MeOH+3 drops TFA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 60:40). The fractions containing products 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 a white solid. (HPLC: tR 2.46 min (Method A); M+H=387 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 11.66 (s, br, 1H), 8.72 (s, 1H), 8.33-8.26 (m, 1H), 8.16-8.10 (m, 1H), 8.09-8.01 (m, 1H), 7.91-7.84 (m, 1H), 7.81-7.74 (m, 1H), 7.51-7.43 (m, 1H), 6.98-6.91 (m, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 1.95 (s, 3H))

Workup

  1. temperatureThe RM was cooled toll
  2. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 60:40)
  3. additionThe fractions containing products
  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-bd2c2ac45dad46efaf2ba82908bcc9b5
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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