Sodium Iodide → 4-Methyl-3-[7-(2-morpholin-4-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzoic acid

HRID 506986Notes

Reaction equation

HRID 506986 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C:13]3[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=3[CH3:22])[C:16]([OH:18])=[O:17])[C:9]2=[O:12])=[CH:4][CH:3]=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[OH-].[Na+]>CC(C)=O>[CH3:22][C:21]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][C:13]=1[N:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][C:2]([O:1][CH2:33][CH2:34][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:3][CH:4]=2)[C:9]1=[O:12]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 670185873-(7-hydroxy-1-oxo-1H-isoquinolin-2-yl)-4-methylbenzoic acid

Product 1

HCID 670185774-Methyl-3-[7-(2-morpholin-4-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzoic acidYield 58.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzoic acid (885 mg) was dissolved in acetone (50 ml), sodium iodide (45 mg) and potassium carbonate (4.14 g) were added followed by 4-(2-chloroethyl) morpholine hydrochloride (1.68 g). The resultant mixture was stirred at 60° C. for 18 hours. 2N NaOH (9.4 ml) was added and stirred for 20 minutes, cooled and the insoluble material removed by filtration. The filtrate was concentrated, acidified to pH 1 with concentrated hydrochloric acid and purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to give 4-methyl-3-[7-(2-morpholin-4-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzoic acid as an oil (720 mg); NMR Spectrum: (DMSOd6) 2.00 (s, 1H), 2.60 (m, 4H), 2.80 (m, 2H), 3.18 (m, 4H), 3.75 (m, 2H), 6.40 (d, 1H), 6.80 (d, 1H), 7.03 (d, 1H), 7.20 (m, 1H), 7.40 (d, 1H), 7.75 (m, 3H); Mass Spectrum: M+H+ 409.

Workup

  1. temperaturecooled
  2. customthe insoluble material removed by filtration
  3. concentrationThe filtrate was concentrated
  4. custompurified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  5. additiona 99:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-f6e36e56a67146fc9feff4d8dda29bd9
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

Loading…