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

HRID 2423427ノート

反応式

HRID 2423427 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
120 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-deefb9cb1d694bcabd8cb9e21aefdbed
出典データセット
uspto-grants-2011_06
特許番号
US07960552B2

反応ノート

読み込み中…