Hydrochloric Acid → 6-[(4-fluorophenyl)methyl]-4-hydroxy-N,N-dimethyl-3,5-dioxo-7,8-dihydro-2H-2,6-naphthyridine-1-carboxamide

HRID 1817297노트

반응식

HRID 1817297 반응식
[CH3:1][NH:2][CH3:3].C[Al](C)C.[F:8][C:9]1[CH:32]=[CH:31][C:12]([CH2:13][N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[C:17]([OH:29])[C:18](=[O:28])[NH:19][C:20]=3[C:24]([O:26]C)=O)[C:15]2=[O:30])=[CH:11][CH:10]=1.Cl>C1COCC1.C(Cl)Cl>[F:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[C:17]([OH:29])[C:18](=[O:28])[NH:19][C:20]=3[C:24]([N:2]([CH3:3])[CH3:1])=[O:26])[C:15]2=[O:30])=[CH:31][CH:32]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 16682925TrimethylaluminumHCID 54692262methyl 6-[(4-fluorophenyl)methyl]-4-hydroxy-3,5-dioxo-7,8-dihydro-2H-2,6-naphthyridine-1-carboxylate

생성물 1

HCID 546922636-[(4-fluorophenyl)methyl]-4-hydroxy-N,N-dimethyl-3,5-dioxo-7,8-dihydro-2H-2,6-naphthyridine-1-carboxamide

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a cooled (−10° C.) solution of dimethylamine (2M in THF, 0.002 g, 0.035 mmol) was slowly added trimethylaluminum (2M in toluene, 0.002 g, 0.035 mmol) and stirred for 30 minutes at room temperature. The reaction mixture was cooled to −10° C. and methyl 6-(4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate (0.004 g, 0.012 mmol, Example 1, Step 8) in THF (5 mL) was added. The reaction stirred at room temperature for 2 hours, then transferred via syringe to a solution of 1:1 CH2Cl2:0.5 N aq. HCl at 0° C. and stirred for 1 hour. The product mixture was separated, and the aqueous was extracted three times with CH2Cl2. The aqueous layer was treated with saturated Na2CO3 solution to pH 5 and extracted three times with CH2Cl2 again. The organic combined extracts were dried with Na2SO4 and concentrated under vacuum. The residue was purified by reverse phase HPLC eluting with 5%-95% acetonitrile (0.1% TFA) in H2O (0.1% TFA) to afford the title compound as a light yellow solid.

후처리

  1. temperatureThe reaction mixture was cooled to −10° C.
  2. stirringThe reaction stirred at room temperature for 2 hours
  3. customThe product mixture was separated
  4. extractionthe aqueous was extracted three times with CH2Cl2
  5. additionThe aqueous layer was treated with saturated Na2CO3 solution to pH 5
  6. extractionextracted three times with CH2Cl2 again
  7. dry with materialThe organic combined extracts were dried with Na2SO4
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by reverse phase HPLC
  10. washeluting with 5%-95% acetonitrile (0.1% TFA) in H2O (0.1% TFA)

출처 및 근거

ORD 기록
ord-d8c2baa637c74c49bd5cb7b1b5425497
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07598264B2

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