Hydrochloric Acid → 3{-[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-2,2-dimethyl-propionic acid

HRID 1481110Notes

Reaction equation

HRID 1481110 reaction equation
C(O[C:6]([C:8]1[N:9]=[C:10]([C:27]#[N:28])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])CCC.C([O:33][C:34](=[O:40])[C:35]([CH3:39])([CH3:38])[CH2:36][NH2:37])(C)(C)C.Cl>CO.O>[C:27]([C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:19][C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)[CH:12]=2)[C:17]([OH:18])=[C:8]([C:6]([NH:37][CH2:36][C:35]([CH3:39])([CH3:38])[C:34]([OH:40])=[O:33])=[O:7])[N:9]=1)#[N:28]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 15430260Tert-butyl 3-amino-2,2-dimethylpropanoateHCID 671101121-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester

Product 1

HCID 898131633{-[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-2,2-dimethyl-propionic acidYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of 1-cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (80 mg, 0.21 mmol) (prepared according to U.S. Pat. No. 7,928,120) and 3-Amino-2,2-dimethyl-propionic acid tert-butyl ester (71 mg, 0.41 mmol) in MeOH (1.5 mL) was microwaved at 120° C. For 1 h. Reaction mixture was diluted with water (80 mL), acidified by 1 N HCl and then extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Residue was then treated with 3 mL of (½) TFA/CH2Cl2. Resultant mixture was stirred at room temperature for 5 h and concentrated to provide the title compound 90 mg (0.21 mmol) in 100% yield. LC-MS ESI−: 422.07 (M−1)−.

Workup

  1. customprepared
  2. customReaction mixture
  3. extractionextracted with EtOAc
  4. washOrganic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionResidue was then treated with 3 mL of (½) TFA/CH2Cl2
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b1b2e39e2f9f4b65b3a5901c632cb290
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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