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

HRID 1481108Notes

Reaction equation

HRID 1481108 reaction equation
C(O[C:4]([C:6]1[N:7]=[C:8]([C:26]#[N:27])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])C.C([O:32][C:33](=[O:39])[C:34]([CH3:38])([CH3:37])[CH2:35][NH2:36])(C)(C)C.C(O)(=O)C>CO>[Cl:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[O:17][C:11]1[CH:10]=[C:9]2[C:14]([C:15]([OH:16])=[C:6]([C:4]([NH:36][CH2:35][C:34]([CH3:38])([CH3:37])[C:33]([OH:39])=[O:32])=[O:5])[N:7]=[C:8]2[C:26]#[N:27])=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 15430260Tert-butyl 3-amino-2,2-dimethylpropanoateHCID 89813167HCID 89813167, compound

Product 1

HCID 717364373-{[7-(2-Chloro-4-fluoro-phenoxy)-1-cyano-4-hydroxy-isoquinoline-3-carbonyl]-amino}-2,2-dimethyl-propionic acidYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of A mixture of 1-cyano-4-hydroxy-7-(4-fluoro-2-chloro-phenoxy)-isoquinoline-3-carboxylic acid ethyl ester (40 mg, 0.10 mmol) and 3-amino-2,2-dimethyl-propionic acid tert-butyl ester (43 mg, 0.25 mmol) in 1 mL of MeOH was microwaved at 130° C. for 1 h. Reaction mixture was quenched with acetic acid (0.3 mmol) and then concentrated. Residue was purified by silica gel chromatography, eluting with 5-60% EtOAc/hexanes, to provide the title compound 41 mg (0.08 mmol) in 80% yield. 1H NMR (200 MHz) in CDCl3, δ ppm: 14.07 (s, 1H), 8.41 (d, J=9.2 Hz, 1H), 8.32 (br t, 1H), 7.50 (dd J=9.1, 2.6 Hz, 1H), 7.38-7.10 (m, 4H), 3.55 (d, J=6.8, 2 H), 1.23 (s, 6H).

Workup

  1. customwas microwaved at 130° C. for 1 h
  2. customReaction mixture
  3. concentrationconcentrated
  4. customResidue was purified by silica gel chromatography
  5. washeluting with 5-60% EtOAc/hexanes

Sources & evidence

ORD record
ord-457226b60d1f4483b702a20b454314cb
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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