Ethyl 3-amino-2,2-dimethylpropanoate → 3-{[1-Cyano-7-(4-fluoro-benzoylamino)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-2,2-dimethyl-propionic acid ethyl ester

HRID 1481170Notes

Reaction equation

HRID 1481170 reaction equation
C(O[C:4]([C:6]1[N:7]=[C:8]([C:27]#[N:28])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([NH:17][C:18](=[O:26])[C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[CH:10]=2)=[O:5])C.[CH2:29]([O:31][C:32](=[O:38])[C:33]([CH3:37])([CH3:36])[CH2:34][NH2:35])[CH3:30]>C(O)C>[CH2:29]([O:31][C:32](=[O:38])[C:33]([CH3:37])([CH3:36])[CH2:34][NH:35][C:4]([C:6]1[N:7]=[C:8]([C:27]#[N:28])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([NH:17][C:18](=[O:26])[C:19]1[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=1)[CH:10]=2)=[O:5])[CH3:30]

Participants

4

Reactant 2

HCID 421529Ethyl 3-amino-2,2-dimethylpropanoateHCID 898131841-Cyano-7-(4-fluoro-benzoylamino)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

Product 1

HCID 898151033-{[1-Cyano-7-(4-fluoro-benzoylamino)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-2,2-dimethyl-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-Cyano-7-(4-fluoro-benzoylamino)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester (70 mg, 0.2636 mmol) was dissolved/suspended in ethanol (4 mL) and 3-Amino-2,2-dimethyl-propionic acid ethyl ester (115 mg, 0.791 mmol) was added via syringe. The reaction was brought to reflux and maintained for 70 h. The reaction was cooled, concentrated and purified by medium pressure liquid chromatography (15 to 50% ethyl acetate in hexanes) to give the product as a white solid which was used immediately in the following reaction.

Workup

  1. temperatureto reflux
  2. temperaturemaintained for 70 h
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated
  5. custompurified by medium pressure liquid chromatography (15 to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bc9affaabe3740f8add917182d12e7c5
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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