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Hydrochloric Acid → 6-[4-({[5-Cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid

HRID 2423434
ノート
印刷プレビュー

反応式

HRID 2423434 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][N: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:26]=[C:27]4[C:32](=[CH:33][CH:34]=3)[N:31]=[C:30]([C:35]([O:37]C)=[O:36])[CH:29]=[CH:28]4)=[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][N: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:26]=[C:27]4[C:32](=[CH:33][CH:34]=3)[N:31]=[C:30]([C:35]([OH:37])=[O:36])[CH:29]=[CH:28]4)=[CH:23][CH:24]=2)[CH2:2][CH2:3]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321467Methyl 6-[4-({[5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

生成物 1

HCID 593214656-[4-({[5-Cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid収率 78%

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 6-[4-({[5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (70 mg, 0.13 mmol) in 2:1 tetrahydrofuran:methanol (1.5 mL) was added 1 N sodium hydroxide (0.19 mL, 0.19 mmol). The solution was heated in a microwave reactor at 120° C. for 500 seconds. Then (0.19 mL, 0.19 mmol) 1 N hydrochloric acid was added and the solution was concentrated. The residue was taken up with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine and concentrated. The resulting solid was dried under a nitrogen stream at 45° C. over 48 hours to afford 6-[4-({[5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid as a yellow solid (53 mg, 78%). 1H-NMR (400 MHz, DMSO-d6) δ 13.37 (br s, 1H), 8.81 (s, 2H), 8.53 (d, J=9 Hz, 1H), 8.28 (s, 1H), 8.18-8.08 (m, 3H), 7.74 (d, J=9 Hz, 2H), 6.92 (d, J=9 Hz, 2H), 5.02 (s, 2H), 2.52-2.46 (m, 1H), 1.23-1.10 (m, 4H). HRMS (ESI) C28H19Cl2N3O4 calculated: 532.0825 [M+H]+, found: 532.0823 [M+H]+.

後処理

  1. concentrationthe solution was concentrated
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. concentrationconcentrated
  5. customThe resulting solid was dried under a nitrogen stream at 45° C. over 48 hours

出典と根拠

ORDレコード
ord-12a5ed4e7aa2403e9718b40f07874c93
出典データセット
uspto-grants-2011_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07960552B2

反応ノート

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