Cesium carbonate → Ethyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)-2-methylpropanoate

HRID 468767Notes

Reaction equation

HRID 468767 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.Br[C:19]([CH3:26])([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C>[CH:15]1([C:13]([NH:12][C:7]2[N:8]=[CH:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([O:1][C:19]([CH3:26])([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:11]=3)=[O:14])[CH2:16][CH2:17]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 312751,4-DioxaneHCID 67975011N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67974885Ethyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)-2-methylpropanoateYield 80.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide (53 mg, 0.23 mmol), ethyl 2-bromoisobutyrate (69 uL, 0.47 mmol), cesium carbonate (166.8 mg, 0.5119 mmol), and 1,4-dioxane (2.0 mL, 26 mmol) was heated in a sealed vial at 100° C. for 22 hours. The reaction mixture was poured into ethyl acetate, washed with water and brine, dried over MgSO4, filtered, and evaporated in vacuo to yield 63.4 mg (80%) of ethyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)-2-methylpropanoate which was carried forward without purification. LCMS (ESI): M+H=343.2.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-e2e01af604464f88aa83c2bf93ae7d9d
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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