Lithium Hydroxide → HCID 44182941, compound

HRID 2069766Notes

Reaction equation

HRID 2069766 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[CH:14][N:13]([CH3:16])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH3:17][N:18]([CH3:50])[C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[C:25](=[O:29])[N:24]([C:30]1[CH:40]=[CH:39][CH:38]=[C:37](B3OC(C)(C)C(C)(C)O3)[C:31]=1[CH2:32][O:33]C(=O)C)[CH:23]=[CH:22]2.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Li+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:17][N:18]([CH3:50])[C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[C:25](=[O:29])[N:24]([C:30]1[CH:40]=[CH:39][CH:38]=[C:37]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:15]=[CH:14][N:13]([CH3:16])[N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=3)[C:31]=1[CH2:32][OH:33])[CH:23]=[CH:22]2

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 59216459HCID 59216459, compoundHCID 592164605-Bromo-1-methyl-3-(1-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one

Product 1

HCID 44182941HCID 44182941, compoundYield 44.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

5-Bromo-1-methyl-3-(1-methyl-1H-pyrazol-3-ylamino)-1H-pyridin-2-one (47 mg, 0.17 mmol), Acetic acid 2-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (77 mg, 0.17 mmol), tetrakis(triphenylphosphine)palladium(0) (19 mg, 0.016 mmol), and sodium carbonate (53 mg, 0.50 mmol) were dissolved in 2 mL 1,2-dimethoxyethane and 1 mL water. This was microwaved at 120° C. for 30 minutes. This was partitioned between ethylacetate and water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. This was dissolved in 3 mL tetrahydrofuran, 1.5 mL methanol, and 1.5 mL water. 1M aq. Lithium hydroxide solution (0.5 mL, 0.5 mmol) was added. This stirred for 3 hours. This was partitioned between ethylacetate and water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by preparative TLC (elution with 5% methanol/dichloromethane) to yield 6-Dimethylamino-2-{2-hydroxymethyl-3-[1-methyl-5-(1-methyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydro-pyridin-3-yl]-phenyl}-2H-isoquinolin-1-one (37 mg, 0.075 mmol). MS (ESI) 497.1 (M+H)+.

Workup

  1. customThis was microwaved at 120° C. for 30 minutes
  2. customThis was partitioned between ethylacetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThis was dissolved in 3 mL tetrahydrofuran
  7. customThis was partitioned between ethylacetate and water
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. custompurified by preparative TLC (elution with 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-bc565d9d6ab64ad7b3b4f80d00f66091
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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