Hydrochloric Acid → 7-[4-({[5-Cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylic acid

HRID 2423427Notes

Reaction equation

HRID 2423427 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:34]=[C:33]4[C:28]([CH:29]=[C:30]([C:35]([O:37]C)=[O:36])[N:31]=[CH:32]4)=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>CO>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:10]([Cl:16])=[CH:11][CH:12]=[CH:13][C:14]=3[Cl:15])[C:5]=2[CH2:17][O:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]3[CH:34]=[C:33]4[C:28]([CH:29]=[C:30]([C:35]([OH:37])=[O:36])[N:31]=[CH:32]4)=[CH:27][CH:26]=3)=[CH:23][CH:24]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321589Methyl 7-[4-({[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylate

Product 1

HCID 593215757-[4-({[5-Cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylic acidYield 68.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 7-[4-({[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylate (54 mg, 0.099 mmol) in 2:1 tetrahydrofuran:methanol (1.5 ml) was added 1 N sodium hydroxide (0.15 mL, 0.15 mmol). The solution was heated in a microwave reactor to 120° C. for 500 seconds. The solution was concentrated under a nitrogen stream and 1 N hydrochloric acid (0.15 mL, 0.15 mmol) was added. The solution was further concentrated under a nitrogen stream. Water and ethyl acetate were added and a solid precipitated that would not dissolve. The water layer was removed and the resulting mixture was washed twice with water. The organic solvents were removed under vacuum and the resulting solid was dried at 45° C. under a nitrogen stream to afford 7-[4-({[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylic acid (36 mg, 68%). 1H-NMR (400 MHz, DMSO-d6) δ 13.1 (br s, 1H), 9.39 (s, 1H), 8.60 (s, 1H), 8.43 (s, 1H), 8.22-8.13 (m, 2H), 7.75 (d, J=9 Hz, 2H), 7.61-7.51 (m, 3H), 6.96 (d, J=9 Hz, 2H), 4.94 (s, 2H), 2.51-2.45 (m, 1H), 1.12-1.13 (m, 4H). HRMS (ESI) C29H20Cl2N2O4 calculated: 531.0880 (M+H)+, found: 531.0872 (M+H)+.

Workup

  1. additionwas added
  2. concentrationThe solution was further concentrated under a nitrogen stream
  3. additionWater and ethyl acetate were added
  4. customa solid precipitated that would not
  5. dissolutiondissolve
  6. customThe water layer was removed
  7. washthe resulting mixture was washed twice with water
  8. customThe organic solvents were removed under vacuum
  9. customthe resulting solid was dried at 45° C. under a nitrogen stream

Sources & evidence

ORD record
ord-deefb9cb1d694bcabd8cb9e21aefdbed
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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