Lithium Hydroxide → HCID 59619627, compound

HRID 445722Notes

Reaction equation

HRID 445722 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:25])[C:13](=[O:24])[N:14]([C:15]4[C:16]([CH3:23])=[N:17][N:18]([CH:20]([CH3:22])[CH3:21])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.C([N:29](C(=O)C)[C:30]1[C:35]([CH2:36][O:37]C(=O)C)=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=1)(=O)C.[Li+].[OH-]>CN(C=O)C.C([O-])([O-])=O.[K+].[K+].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>[NH2:29][C:30]1[N:31]=[CH:32][C:33]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]([CH3:25])[C:13](=[O:24])[N:14]([C:15]5[C:16]([CH3:23])=[N:17][N:18]([CH:20]([CH3:21])[CH3:22])[CH:19]=5)[C:5]=4[C:4]=3[CH:3]=2)=[CH:34][C:35]=1[CH2:36][OH:37]

Participants

7

Reactant 3

HCID 3939Lithium HydroxideHCID 59613015HCID 59613015, compoundHCID 596200788-bromo-1-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one2×

Product 1

HCID 59619627HCID 59619627, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 8-bromo-1-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Intermediate G, 0.098 mmol), crude acetic acid 2-diacetylamino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-ylmethyl ester (stage 169.1.1, 0.92 mg) and PdCl2(PPh3)2 (0.0057 mmol) in DMF (1.2 ml) and 1 M aqueous K2CO3 (0.245 ml) was stirred under argon at 105° C. for 1 h. Then the RM was cooled to it and 2 M aqueous LiOH (0.245 ml) was added. The RM was stirred for 1 h 15 min at rt then quenched with 2 M aqueous HCl (0.245 ml), diluted with MeOH and purified directly by Prep.HPLC. The fractions containing product were collected together, basified with NaHCO3, concentrated and extracted with dichloromethane (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered, evaporated and dried under vacuum to give the title compound as a white solid. (HPLC: tR 2.04 min (Method A); M+H=444 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.91 (s, 1H), 8.20 (s, 1H), 8.06-8.02 (m, 1H), 7.97-7.94 (m, 1H), 7.83-7.78 (m, 1H), 7.57-7.54 (m, 1H), 7.45-7.42 (m, 1H), 5.95 (s, br, 2H), 5.20 (t, 1H), 4.55 (hp, 1H), 4.37 (d, 2H), 3.57 (s, 3H), 1.95 (s, 3H), 1.47 (d, 6H))

Workup

  1. additionwas added
  2. stirringThe RM was stirred for 1 h 15 min at rt
  3. customthen quenched with 2 M aqueous HCl (0.245 ml)
  4. additiondiluted with MeOH
  5. custompurified directly by Prep.HPLC
  6. additionThe fractions containing product
  7. customwere collected together
  8. concentrationconcentrated
  9. extractionextracted with dichloromethane (2×)
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated
  14. customdried under vacuum

Sources & evidence

ORD record
ord-c6f6712cb11046198526b3865bb0f8aa
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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