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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
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HRID 2423434 반응식
[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
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6

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

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온도
120 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-12a5ed4e7aa2403e9718b40f07874c93
출처 데이터셋
uspto-grants-2011_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07960552B2

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