Acetone → 4-Methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzoic acid

HRID 506988Notes

Reaction equation

HRID 506988 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.ClCC[CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.[OH-].[Na+].[CH3:43][C:44](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][CH2:43][CH2:44][N:38]3[CH2:37][CH2:36][CH2:35][CH2:40][CH2:39]3)=[CH:3][CH:4]=2)[C:9]1=[O:12]

Participants

7

Reactant 6

HCID 180AcetoneHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 219374464-(2-Chloroethyl)piperidine hydrochlorideHCID 670185873-(7-hydroxy-1-oxo-1H-isoquinolin-2-yl)-4-methylbenzoic acid

Product 1

HCID 670185784-Methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzoic acid

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)piperidine hydrochloride (1.67 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-piperidin-1-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzoic acid as an oil (205 mg); NMR Spectrum: (DMSOd6) 2.13 (s, 1H), 3.00 (m, 4H), 3.35 (m, 2H), 3.95 (m, 4H), 4.58 (m, 2H), 6.46 (d, 1H), 6.90 (d, 1H), 7.25 (m, 1H), 7.35 (m, 1H), 7.50 (d, 1H), 7.80 (d, 1H), 7.87 (d, 1H), 7.98 (m, 1H); Mass Spectrum: M+H+ 407.

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-8a757d5276234da2ad3e2133b9a5c914
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

Loading…