Hydrochloric Acid → 1-Benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1411059노트

반응식

HRID 1411059 반응식
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9](Br)=[CH:8]2)=[O:4].[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.CCOC(C)=O.O>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:30]1[CH:31]=[CH:32][C:27]([C:26]([F:37])([F:36])[F:25])=[CH:28][CH:29]=1)=[CH:8]2)=[O:4]

참가 물질

10

반응물 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

생성물 1

HCID 682971661-Benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester수율 65.2%

시약·촉매·용매 5

HCID 167845palladium(II) acetate촉매HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl촉매HCID 962Water용매2회HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
105 °C

실험 절차

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (220 mg, 0.57 mmol), 4-(trifluoromethyl)phenylboronic acid (161 mg, 0.85 mmol), K3PO4 (240 mg, 1.13 mmol), H2O (20 mg, 1.13 mmol), SPhos (12 mg, 0.028 mmol) and Pd(OAc)2 (12 mg, 0.017 mmol) in toluene (10 mL) was heated at 105° C. under nitrogen atmosphere for 20 h. After the mixture was cooled to r.t., water and EtOAc were added. 1 M HCl was added until pH was about 3, and the aqueous layer was extracted with additional EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH) to give 169 mg of the title compound as a yellow solid. MS: (+) m/z 455.34 (M+1).

후처리

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionthe aqueous layer was extracted with additional EtOAc
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH)

출처 및 근거

ORD 기록
ord-2a5215969cd64bd59c9dbd8483dbe515
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921389B2

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