Lithium Hydroxide → HCID 44183073, compound

HRID 2069767

Reaction equation

HRID 2069767 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[C:8](=[O:23])[N:9]([CH3:22])[CH:10]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:12]=1)=[O:5])[CH3:2].Br[C:25]1[CH:35]=[CH:34][CH:33]=[C:32]([N:36]2[CH:45]=[CH:44][C:43]3[C:38](=[CH:39][CH:40]=[C:41]([N:46]([CH3:48])[CH3:47])[CH:42]=3)[C:37]2=[O:49])[C:26]=1[CH2:27][O:28]C(=O)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Li+]>>[CH3:47][N:46]([CH3:48])[C:41]1[CH:42]=[C:43]2[C:38](=[CH:39][CH:40]=1)[C:37](=[O:49])[N:36]([C:32]1[C:26]([CH2:27][OH:28])=[C:25]([C:11]3[CH:12]=[C:7]([NH:6][C:4]([NH:3][CH2:1][CH3:2])=[O:5])[C:8](=[O:23])[N:9]([CH3:22])[CH:10]=3)[CH:35]=[CH:34][CH:33]=1)[CH:45]=[CH:44]2

Participants

5

Reactant 4

HCID 3939Lithium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 59216403Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-benzyl esterHCID 68496761HCID 68496761, compound

Product 1

HCID 44183073HCID 44183073, compoundYield 42.5%

Conditions

Temperature
100 °C

Procedure

To 1-Ethyl-3-[1-methyl-2-oxo-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2-dihydro-pyridin-3-yl]-urea (50 mg, 0.16 mmol), acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-benzyl ester (65 mg, 0.16 mmol), potassium phosphate (66 mg, 0.31 mmol), 2-(dicyclohexylphoshphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (4.4 mg, 0.0092 mmol), and bis(dibenzylidineacetone)palladium(0) (2.6 mg, 0.0045 mmol) was added 4 mL of degassed 1:3 water/n-butanol. The headspace of the vessel was evacuated and backfilled with argon 4 times. This was heated at 100° C. for 2 hours. This was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. This was dissolved in 2 mL tetrahydrofuran, 1 mL methanol, and 1 mL water. 1M aq. lithium hydroxide solution (0.47 mL, 0.47 mmol) was added. After stirring for 3 hours, the resulting mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by preparative TLC (5% methanol/dichloromethane) to yield 1-{5-[3-(6-Dimethylamino-1-oxo-1H-isoquinolin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl}-3-ethyl-urea (33 mg, 0.068 mmol). MS (ESI) 488.1(M+H)+.

Workup

  1. customof degassed 1:3 water/n-butanol
  2. customThe headspace of the vessel was evacuated
  3. customThis was partitioned between ethyl acetate and water
  4. washThe ethyl acetate layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThis was dissolved in 2 mL tetrahydrofuran
  8. customthe resulting mixture was partitioned between ethyl acetate and water
  9. washThe ethyl acetate layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. custompurified by preparative TLC (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-da5b640e885b4b1a92b8b0b5ad944a5a
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Linked notes

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