Glycine → [(1-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid

HRID 409200Notes

Reaction equation

HRID 409200 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][CH2:26][C:27]([OH:29])=[O:28].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][CH2:26][C:27]([OH:29])=[O:28])=[O:4])[N:6]=1)#[N:24]

Participants

5

Reactant 3

HCID 750GlycineHCID 10942334Sodium MethoxideHCID 671101071-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 24780125[(1-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acidYield 97.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1-cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester (322 mg, 1.0 mmol), glycine (1.51 g, 20.1 mmol), and a 0.5 M sodium methoxide solution in methanol (38.2 mL) was refluxed for 31 h before it was cooled to room temperature and concentrated in vacuo. Water (75 mL) was added and the pH of the yellow suspension was adjusted to 10 with aqueous 1 N HCl. A clear yellow solution was obtained after 5 minutes of sonication. The solution was washed with dichloromethane (2×50 mL). The remaining aqueous layer was acidified to pH=3 with aqueous 1 N HCl. The white precipitate formed was separated by filtration, washed with water and dried in vacuo to give the title compound as a white solid (354 mg): 1H NMR (DMSO-d6, 200 MHz): δ=12.86 (bs, 1H), 9.56 (t, 1H), 8.09 (m, 1H), 7.88 (t, J=8.2 Hz, 1H), 7.47 (m, 2H), 7.21 (m, 4H), 4.05 (d, J=5.8 Hz, 2H).

Workup

  1. concentrationconcentrated in vacuo
  2. additionWater (75 mL) was added
  3. customA clear yellow solution was obtained after 5 minutes of sonication
  4. washThe solution was washed with dichloromethane (2×50 mL)
  5. customThe white precipitate formed
  6. customwas separated by filtration
  7. washwashed with water
  8. customdried in vacuo

Sources & evidence

ORD record
ord-171ff3023ca24eb19119ae37a1aef224
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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