Hydrochloric Acid → N-cyclopropyl-3-(7-hydroxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide

HRID 507004Notes

Reaction equation

HRID 507004 reaction equation
[CH:1]1([NH:4][C:5](=[O:27])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:22]=[C:21]([CH3:23])[C:20]4[C:15](=[CH:16][C:17]([O:24]C)=[CH:18][CH:19]=4)[C:14]3=[O:26])[CH:7]=2)[CH2:3][CH2:2]1.[I-].[Li+].Cl>N1C(C)=CC(C)=CC=1C.[OH-].[Na+]>[CH:1]1([NH:4][C:5](=[O:27])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:22]=[C:21]([CH3:23])[C:20]4[C:15](=[CH:16][C:17]([OH:24])=[CH:18][CH:19]=4)[C:14]3=[O:26])[CH:7]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 66321Lithium iodideHCID 11710269N-cyclopropyl-3-(7-methoxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide

Product 1

HCID 67018616N-cyclopropyl-3-(7-hydroxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 79532,4,6-TrimethylpyridineSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
200 °C

Procedure

N-cyclopropyl-3-(7-methoxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide (262 mg, 0.72 mmol) and lithium iodide (174 mg) were stirred in 2,4,6-collidine (3 ml) and heated under microwave irradiation conditions (Personal Chemistry Emrys Optimizer with 300 W magnetron) at 200° C. for 1.5 hour and then allowed to cool. The reaction mixture was dissolved in 2N NaOH and then re-acidified with 2N HCl solution. The aqueous phase was extracted with ethyl acetate (×4) and the combined organic layers were concentrated. The residue was triturated with 1N HCl, the solid was collected by filtration, washed with water, diethyl ether, and air dried to give N-cyclopropyl-3-(7-hydroxy-4-methyl-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide as an off white solid (207 mg); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.69 (m, 2H), 2.09 (s, 3H), 2.24 (s, 3H), 2.86 (m, 1H), 7.00 (s, 1H), 7.31 (d, 1H), 7.48 (d, 1H), 7.62-7.65 (m, 2H), 7.74 (s, 1H), 7.85 (d, 1H), 8.45 (d, 1H), 10.04 (s, 1H); Mass Spectrum: M+H+ 349.

Workup

  1. temperatureto cool
  2. extractionThe aqueous phase was extracted with ethyl acetate (×4)
  3. concentrationthe combined organic layers were concentrated
  4. customThe residue was triturated with 1N HCl
  5. filtrationthe solid was collected by filtration
  6. washwashed with water, diethyl ether, and air
  7. customdried

Sources & evidence

ORD record
ord-f1e1dbf5f39a4032b802a64ee6ee4a86
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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