(6-Methoxypyridin-3-yl)boronic acid → HCID 49835667, compound

HRID 445661Notes

Reaction equation

HRID 445661 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:26])[C:13](=[O:25])[N:14]([C:15]4[C:16]([CH3:24])=[N:17][N:18]([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=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>[CH3:27][O:28][C:29]1[N:30]=[CH:31][C:32]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]([CH3:26])[C:13](=[O:25])[N:14]([C:15]5[C:16]([CH3:24])=[N:17][N:18]([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=5)[C:5]=4[C:4]=3[CH:3]=2)=[CH:33][CH:34]=1

Participants

7

Reactant 2

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 596200051H-Pyrazole-1-acetic acid, 4-(8-bromo-2,3-dihydro-3-methyl-2-oxo-1H-imidazo[4,5-c]quinolin-1-yl)-3-methyl-

Product 1

HCID 49835667HCID 49835667, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
105 °C

Procedure

A mixture of [4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-3-methyl-pyrazol-1-yl]-acetic acid (Stage 101.1.1b, 161 mg, 0.387 mmol), 2-methoxypyridine-5-boronic acid (Aldrich, Buchs, Switzerland, 77 mg, 0.503 mmol), and PdCl2(PPh3)2 (17 mg, 0.024 mmol) in DMF (4.0 ml) and 1 M aqueous K2CO3 (1.16 ml) was stirred under argon at 105° C. for 1.25 h. The RM was cooled to rt. The mixture was diluted with MeOH+3 drops TFA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35). The fractions containing products were collected together concentrated, before being lyophilized to give the title compound as a TFA-salt and white powder. (HPLC: tR 2.38 min (Method A); M+H=446 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 9.22 (s, 1H), 8.46 (s, 1H), 8.23-8.14 (m, 3H), 7.87-7.79 (m, 1H), 7.74-7.68 (m, 1H), 6.94-6.88 (m, 1H), 5.15-4.98 (m, 2H), 3.89 (s, 3H), 3.60 (s, 3H), 1.97 (s, 3H))

Workup

  1. temperatureThe RM was cooled to rt
  2. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35)
  3. additionThe fractions containing products
  4. customwere collected together
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-adcfa3ca71994302ac06eb1969f8dfc9
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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