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

HRID 409290Notes

Reaction equation

HRID 409290 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 3

HCID 71080D-AlanineHCID 23694274Sodium methanolate methanolHCID 671101071-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 67110268(R)-2-[(1-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-propionic acidYield 79.5%

Procedure

A mixture of 1-cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester (95 mg, 0.30 mmole), D-Alanine (529 mg, 5.94 mmole) and 0.5 M sodium methoxide/methanol (11.3 mL) was refluxed for three days before it was cooled to room temperature and concentrated in vacuo. The residue was dissolved in water (25 mL) and extracted with dichloromethane (3×30 mL). The remaining aqueous layer was acidified to pH=3 with 1N HCl (8 mL). The white suspension was extracted with ethyl acetate (30 mL) and dichloromethane (30 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo to give the title compound as a white solid (90 mg): 1H NMR (DMSO-d6, 200 MHz): δ=13.52 (bs, 1H), 9.15 (br s, 1H), 8.30 (d, 1H), 8.10 (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=7.0 Hz, 3H)); MS: (+) m/z 378.29 (M+1).

Workup

  1. temperaturewas refluxed for three days before it
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in water (25 mL)
  4. extractionextracted with dichloromethane (3×30 mL)
  5. extractionThe white suspension was extracted with ethyl acetate (30 mL) and dichloromethane (30 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ef0a7caf8ac4206b4169d4c1f2bba91
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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