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

HRID 2423427Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2423427
[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

Komponenten

6

Edukt 4

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

Produkt 1

HCID 593215757-[4-({[5-Cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylic acidAusbeute 68,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

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)+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-deefb9cb1d694bcabd8cb9e21aefdbed
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07960552B2

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