4-Bromo-2-fluoroaniline → 2-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

HRID 15938

반응식

HRID 15938 반응식
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](=[O:11])[N:7]([CH3:12])[C:6]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=1[F:21])=[O:4].BrC1C=CC(N)=C(F)C=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].COC(C1C=CC(=O)N(C)C=1Cl)=O>C1COCC1>[Br:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:6]2[N:7]([CH3:12])[C:8](=[O:11])[CH:9]=[CH:10][C:5]=2[C:3]([OH:4])=[O:2])=[C:15]([F:21])[CH:16]=1

참가 물질

6

반응물 4

HCID 1230504-Bromo-2-fluoroanilineHCID 2733832Lithium HexamethyldisilazideHCID 57442171Methyl 2-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylateHCID 66673525Methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

생성물 1

HCID 576369362-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid수율 65%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

Preparation of 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester: To a solution of 4-bromo-2-fluorophenylamine (0.192 g, 1.01 mmol) in THF (5 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (1.50 mL, 1.50 mmol, 1 M solution in hexanes) dropwise. The reaction mixture was stirred for one hour at −78° C. 2-Chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester (0.202 g, 1.00 mmol) was then added dropwise as a solution in THF (5 mL) and the reaction mixture was stirred for one hour at −78° C. The reaction mixture was quenched by the addition of H2O and the pH was adjusted to pH 7 with saturated NH4Cl and then diluted with EtOAc. The organic layer was separated and washed with saturated NaCl, dried (Na2SO4), and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave 0.232 g (65%) pure desired product as a white crystalline solid.

후처리

  1. stirringthe reaction mixture was stirred for one hour at −78° C
  2. customThe reaction mixture was quenched by the addition of H2O
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with saturated NaCl
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)

출처 및 근거

ORD 기록
ord-a7bb07a7451d4d20b7ec436a7e36c3c0
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732616B2

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