Triethylamine → [(1-Cyano-4-methoxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid methyl ester

HRID 706219Notes

Reaction equation

HRID 706219 reaction equation
[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:6]([O:20][CH3:21])=[C:5]([C:22]([OH:24])=O)[N:4]=1)#[N:2].C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.Cl.[CH3:41][O:42][C:43](=[O:46])[CH2:44][NH2:45]>ClCCl>[CH3:41][O:42][C:43](=[O:46])[CH2:44][NH:45][C:22]([C:5]1[N:4]=[C:3]([C:1]#[N:2])[C:12]2[C:7]([C:6]=1[O:20][CH3:21])=[CH:8][CH:9]=[CH:10][C:11]=2[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:24]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 122755Glycine methyl ester hydrochlorideHCID 671101241-Cyano-4-methoxy-8-phenoxy-isoquinoline-3-carboxylic acid

Product 1

HCID 24780690[(1-Cyano-4-methoxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid methyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 1-cyano-4-methoxy-8-phenoxy-isoquinoline-3-carboxylic acid (483 mg, 1.51 mmol), triethylamine (466 μL, 3.32 mmol), and dichloromethane (12 mL) was added isobutylchloroformate (211 μL, 1.62 mmol) at 0° C. The mixture was stirred at 0° C. for twenty-five minutes before glycine methyl ester hydrochloride (208 mg, 1.66 mmol) was added. The mixture was stirred at 0° C. for twenty-five minutes and at room temperature for 5.5 hours before it was concentrated. The residue was partitioned between ethyl acetate and 1N HCl. The organic layer was washed with saturated sodium bicarbonate, brine, dried over anhydrous sodium sulfate, concentrated in vacuo and the residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and hexanes to give the title compound as a yellow solid (343 mg): MS: (+) m/z 391.95 (M+1).

Workup

  1. additionwas added
  2. concentrationwas concentrated
  3. customThe residue was partitioned between ethyl acetate and 1N HCl
  4. washThe organic layer was washed with saturated sodium bicarbonate, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-501564f202824cc78ecbab00ab01eaab
Source dataset
uspto-grants-2015_11
Patent number
US09174976B2

Reaction notes

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