Acetic Acid → HCID 89813173, compound

HRID 1481197Notes

Reaction equation

HRID 1481197 reaction equation
C(O[C:6]([C:8]1[N:9]=[C:10]([C:26]#[N:27])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[CH:12]=2)=[O:7])CCC.[C:28]([O:32][C:33](=[O:39])[C:34]([CH3:38])([CH3:37])[CH2:35][NH2:36])([CH3:31])([CH3:30])[CH3:29].C(O)(=O)C>C(O)C>[C:28]([O:32][C:33](=[O:39])[C:34]([CH3:38])([CH3:37])[CH2:35][NH:36][C:6]([C:8]1[N:9]=[C:10]([C:26]#[N:27])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[CH:12]=2)=[O:7])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 15430260Tert-butyl 3-amino-2,2-dimethylpropanoateHCID 89813208HCID 89813208, compound

Product 1

HCID 89813173HCID 89813173, compoundYield 98.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-cyano-7-cyclohexyloxy-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (45 mg, 0.12 mmol) (prepared according to U.S. Pat. No. 7,629,357) and 3-amino-2,2-dimethyl-propionic acid tert-butyl ester (50 mg, 0.29 mmol) in ethanol was microwaved at 140° C. for 1 h. Reaction mixture was quenched with acetic acid (3 equivalents) and concentrated. Residue was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexanes to provide the title compound 55 mg (0.118 mmol) in 98% yield. 1H NMR (200 MHz) CDCl3, δ in ppm: 13.92 (s, 1H), 8.29 (d, J=8.4 Hz, 1H), 7.42 (m, 2H), 4.56 (br s, 1H), 3.55 (d, J=6.2 Hz, 2H), 2.04 (br m, 2H), 1.83 (br m, 2H), 1.56-1.24 (m, 21H).

Workup

  1. customprepared
  2. customReaction mixture
  3. concentrationconcentrated
  4. customResidue was purified by silica gel chromatography
  5. washeluting with 5-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-f5475d7d615c42bba520e0c5dc837b75
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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