Acetic Acid → 4-Hydroxy-7-(pyridin-2-yloxy)-isoquinoline-3-carboxylic acid methyl ester

HRID 1480978Notes

Reaction equation

HRID 1480978 reaction equation
C([O:3][C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:6]=1[CH2:18][N:19]([CH2:30][C:31]([O:33][CH3:34])=[O:32])S(C1C=CC(C)=CC=1)(=O)=O)C.C[O-].[Na+].CC(O)=O>CN(C=O)C>[CH3:34][O:33][C:31]([C:30]1[N:19]=[CH:18][C:6]2[C:5]([C:4]=1[OH:3])=[CH:10][CH:9]=[C:8]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[CH:7]=2)=[O:32]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10942334Sodium MethoxideHCID 898129952-{[Methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-4-(pyridin-2-yloxy)-benzoic acid ethyl ester

Product 1

HCID 898129234-Hydroxy-7-(pyridin-2-yloxy)-isoquinoline-3-carboxylic acid methyl esterYield 55.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-{[methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-4-(pyridin-2-yloxy)-benzoic acid ethyl ester (745 mg), and NaOMe (0.702 mL, 0.5 M solution in HOMe) in DMF (5 mL) was stirred with ice/water bath cooling for 4 h. HOAc (2.5 eq relative to NaOMe) was added, diluted with ice/water; then the solids were collected via filtration and washed with water to give product (247 mg). Filtrate was back extracted with EtOAc; EtOAc phase was washed with water, diluted NaCl solution and dried over anhydrous sodium sulphate, filtered, concentrated and column purified to give more product (135 mg). LC MS ESI+: 297 (M+1)+.

Workup

  1. temperaturecooling for 4 h
  2. filtrationthen the solids were collected via filtration
  3. washwashed with water

Sources & evidence

ORD record
ord-f623deed0a5f4c65a42235df711f001e
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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