Sodium hydride → HCID 59563762, compound

HRID 1944161Notes

Reaction equation

HRID 1944161 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:18]([NH:20][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[N:26][CH:25]=[CH:24]3)=[O:19])[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:34][C:35]([O:37][CH3:38])=[O:36]>CN(C=O)C>[C:13]([O:12][C:11]([NH:10][CH2:9][CH:8]([C:5]1[CH:6]=[CH:7][C:2]([O:1][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[CH:3][CH:4]=1)[C:18]([NH:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[CH:27]=[N:26][CH:25]=[CH:24]2)=[O:19])=[O:17])([CH3:14])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 59563693HCID 59563693, compound

Product 1

HCID 59563762HCID 59563762, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-35 °C

Procedure

Methyl 2-(4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)phenoxy)acetate (E250) was prepared from E249 according to the scheme in FIG. 14. To tert-butyl 2-(4-hydroxyphenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate (E249) in DMF cooled to −35° C. was added NaH, and the solution was stirred at −35° C. for 30 min. Then, methyl bromoacetate was added and the solution was warmed and stirred at 0° C. for 1 h. The solution was poured into NaHCO3(sat)/EtOAc and further extracted with EtOAc. The combined organics were dried (Na2SO4), filtered, and evaporated. Column chromatography (SiO2, 3-4% MeOH/CH2Cl2) gave pure methyl 2-(4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)phenoxy)acetate (E250).

Workup

  1. customMethyl 2-(4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)phenoxy)acetate (E250) was prepared from E249
  2. temperaturethe solution was warmed
  3. stirringstirred at 0° C. for 1 h
  4. extractionfurther extracted with EtOAc
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-98585d4d08a6486fa52dbe9dfc867c4c
Source dataset
uspto-grants-2013_03
Patent number
US08394826B2

Reaction notes

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