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

HRID 2423457ノート

反応式

HRID 2423457 の反応式
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11][C:12]3[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:19])[C:6]=2[CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:37]=[C:36]4[C:31]([CH:32]=[C:33]([C:38]([O:40]C)=[O:39])[N:34]=[CH:35]4)=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)[CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>CO>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11][C:12]3[C:13]([CH3:19])=[CH:14][CH:15]=[CH:16][C:17]=3[CH3:18])[C:6]=2[CH2:20][O:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:37]=[C:36]4[C:31]([CH:32]=[C:33]([C:38]([OH:40])=[O:39])[N:34]=[CH:35]4)=[CH:30][CH:29]=3)=[CH:26][CH:27]=2)[CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321545Methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylate

生成物 1

HCID 593214847-(4-{[(5-Cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylic acid収率 84.3%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
100 °C

実験手順

To a solution of methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylate (50 mg, 0.091 mmol) in 2:1 tetrahydrofuran:methanol (3 mL) was added 1 N sodium hydroxide (0.14 mL, 0.14 mmol). The solution was heated in a microwave reactor at 100° C. for 500 seconds. Then 1 N hydrochloric acid (0.14 mL, 0.14 mmol) was added and the mixture was concentrated. The residue was taken up with ethyl acetate and water. The layers were separated and the organic layer was washed with water, dried over magnesium sulfate and concentrated to afford 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylic acid (41 mg, 84%). 1H-NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.61 (s, 1H), 8.49 (s, 1H), 8.24-8.18 (m, 2H), 7.85 (d, J=9 Hz, 2H), 7.16 (d, J=9 Hz, 2H), 7.00-6.90 (m, 3H), 5.06 (s, 2H), 4.90 (s, 2H), 4.01-3.90 (m, 1H), 2.39-2.30 (m, 4H), 2.14 (s, 6H), 2.10-2.00 (m, 1H), 1.90-1.89 (m, 1H). HRMS (ESI) C33H30N2O5 calculated: 535.2228 (M+H)+, found: 535.2228 (M+H)+.

後処理

  1. concentrationthe mixture was concentrated
  2. customThe layers were separated
  3. washthe organic layer was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-79e5ba80a50344609602fa04e8c24274
出典データセット
uspto-grants-2011_06
特許番号
US07960552B2

反応ノート

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