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

HRID 506963Notes

Reaction equation

HRID 506963 reaction equation
[CH:1]1([NH:4][C:5](=[O:26])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([O:23]C)=[CH:18][CH:19]=4)[C:14]3=[O:25])[CH:7]=2)[CH2:3][CH2:2]1.[I-].[Li+].[OH-].[Na+].Cl>N1C(C)=CC(C)=CC=1C>[CH:1]1([NH:4][C:5](=[O:26])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([OH:23])=[CH:18][CH:19]=4)[C:14]3=[O:25])[CH:7]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66321Lithium iodideHCID 11530361N-cyclopropyl-3-(7-methoxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide

Product 1

HCID 11515516N-Cyclopropyl-3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamideYield 69.3%

Reagents, catalysts & solvents 1

HCID 79532,4,6-TrimethylpyridineSolvent

Conditions

Temperature
200 °C

Procedure

A stirred suspension of N-cyclopropyl-3-(7-methoxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide (845 mg) and lithium iodide (585 mg) in 2,4,6 collidine (10 ml) was heated under microwave irradiation conditions (Personal Chemistry Emrys Optimizer with 300 W magnetron) at 200° C. for 90 minutes. The mixture was dissolved using 2N NaOH and re-acidified using 2N HCl. The aqueous phase was extracted with ethyl acetate (×4) and the combined organic layers concentrated. The residue was triturated with 2N HCl and the solid collected by filtration, washed with diethyl ether and air dried to yield N-cyclopropyl-3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzamide as a brown solid (562 mg); NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.69 (m, 2H), 2.10 (s, 3H), 2.85 (m, 1H), 6.66 (d, 1H), 7.11 (d, 1H), 7.24 (d, 1H), 7.49 (d, 1H), 7.60 (s, 1H), 7.61 (d, 1H), 7.73 (s, 1H), 7.88 (d, 1H), 8.43 (d, 1H), 10.00 (s, 1H); Mass Spectrum: M+Na+ 357.

Workup

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

Sources & evidence

ORD record
ord-3152026f5c564506847015f18324cd8e
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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