L-Alanine → (S)-2-[(1-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-propionic acid

HRID 409289Notes

Reaction equation

HRID 409289 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:4].[NH2:25][C@H:26]([C:28]([OH:30])=[O:29])[CH3:27]>C[O-].[Na+].CO>[C:23]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:25][C@@H:26]([CH3:27])[C:28]([OH:30])=[O:29])=[O:4])[N:6]=1)#[N:24]

Participants

4

Reactant 2

HCID 5950L-AlanineHCID 671101071-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 42635865(S)-2-[(1-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-propionic acidYield 100%

Reagents, catalysts & solvents 1

HCID 23694274Sodium methanolate methanolSolvent

Procedure

A mixture of 1-cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester (101 mg, 0.31 mmol) and L-Alanine (561 mg, 6.29 mmol) in 0.5 M sodium methoxide/methanol (12 mL) was refluxed for four days before it was cooled to room temperature and concentrated in vacuo. The residue was dissolved in water (20 mL) and extracted with methyl t-butyl ether (2×30 mL). The remaining aqueous layer was acidified to pH=3 with 1N HCl (8 mL). The resulting white suspension was extracted with ethyl acetate (30 mL), dried and concentrated in vacuo to give the title compound as a white solid (117 mg): 1H NMR (DMSO-d6, 200 MHz): δ=13.52 (bs, 1H), 10.11 (br s, 1H), 8.30 (d, 1H), 8.07 (m, 1H), 7.67 (t, J=8 Hz, 1H), 7.42 (m, 2H), 7.17 (m, 3H), 4.83 (q, 1H), 1.68 (d, J=7.4 Hz); MS: (+) m/z 378.29 (M+1).

Workup

  1. temperaturewas refluxed for four days before it
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in water (20 mL)
  4. extractionextracted with methyl t-butyl ether (2×30 mL)
  5. extractionThe resulting white suspension was extracted with ethyl acetate (30 mL)
  6. customdried
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-617915848ba242a0898303797900ed75
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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