Thionyl Chloride → 4-Hydroxy-7-(pyridin-3-yloxy)-isoquinoline-3-carboxylic acid ethyl ester

HRID 1480973Notes

Reaction equation

HRID 1480973 reaction equation
C([O:3][C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[CH:7][C:6]=1[CH2:18][N:19](CC1C=CC(OC)=CC=1OC)[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])C.CCC([O-])(C)C.[K+].S(Cl)(Cl)=O>C1COCC1.C(Cl)Cl>[CH2:24]([O:23][C:21]([C:20]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:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[CH:7]=2)=[O:22])[CH3:25]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 23683543Potassium t-amylateHCID 898130942-{[(2,4-Dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-4-(pyridin-3-yloxy)-benzoic acid ethyl ester

Product 1

HCID 898130784-Hydroxy-7-(pyridin-3-yloxy)-isoquinoline-3-carboxylic acid ethyl esterYield 64.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To an ice-water bath cooled solution of 2-{[(2,4-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-4-(pyridin-3-yloxy)-benzoic acid ethyl ester (1.71 g) in THF (30 mL) was added a solution of potassium tert-pentoxide (3.36 mL, 1.7 M in toluene); the mixture was stirred for 60 min at rt after addition; then the mixture was quenched with 2 M HCl, diluted with EtOAc and water, EtOAc phase was separated and washed with water, diluted NaCl solution and dried over anhydrous sodium sulphate, filtered off, concentrated to give the desired cyclized intermediate. This intermediate was then dissolved in DCM (30 mL) and treated with thionyl chloride (0.47 mL) overnight. Then concentrated, the residue was dissolved in EtOAc, washed with water, diluted NaCl solution, then dried over sodium sulphate, filtered, concentrated and the residue was column purified to give the desired product (673 mg). LC MS ESI: 311 (M+1)+.

Workup

  1. additionafter addition
  2. customthen the mixture was quenched with 2 M HCl
  3. additiondiluted with EtOAc and water, EtOAc phase
  4. customwas separated
  5. washwashed with water, diluted NaCl solution
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered off
  8. concentrationconcentrated
  9. customto give the
  10. concentrationThen concentrated
  11. dissolutionthe residue was dissolved in EtOAc
  12. washwashed with water, diluted NaCl solution
  13. dry with materialdried over sodium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. custompurified

Sources & evidence

ORD record
ord-1a7996bf17684d8ea4eed6970c625ef8
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

Loading…