Lithium Hydroxide → HCID 44182940, compound

HRID 2069759Notes

Reaction equation

HRID 2069759 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)[CH2:23][CH2:22]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])[CH2:23][CH2:22]2

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 592164605-Bromo-1-methyl-3-(1-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-oneHCID 59216471HCID 59216471, compound

Product 1

HCID 44182940HCID 44182940, compoundYield 60%

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 (35 mg, 0.13 mmol), acetic acid 2-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (58 mg, 0.13 mmol), tetrakis(triphenylphosphine)palladium(0) (14 mg, 0.012 mmol), and sodium carbonate (40 mg, 0.38 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 (0.38 mL, 0.38 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 (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}-3,4-dihydro-2H-isoquinolin-1-one (39 mg, 0.078 mmol). MS (ESI) 499.2 (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 (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-3d2f2b2ba0334e1ca7b5fc07b9a4c064
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

Loading…