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

HRID 15944

반응식

HRID 15944 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:17]=[C:16](Cl)[CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])=[C:4]([F:19])[CH:3]=1.BrC1C=CC(N)=C(F)C=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].ClC1N=C(Cl)C=CC=1C(O)=[O:43]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[NH:17][C:16](=[O:43])[CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])=[C:4]([F:19])[CH:3]=1

참가 물질

6

반응물 4

HCID 1230504-Bromo-2-fluoroanilineHCID 8540472,6-Dichloronicotinic acidHCID 2733832Lithium HexamethyldisilazideHCID 635290422-(4-Bromo-2-fluorophenylamino)-6-chloro-nicotinic acid

생성물 1

HCID 576368232-(4-Bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acid수율 83%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

Preparation of 2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid: To a solution of 4-bromo-2-fluorophenylamine (10.4 g, 54.7 mmol) in THF (25 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (83.3 mL, 83.3 mmol, 1 M solution in hexanes) dropwise over 15 minutes. The reaction mixture was stirred for one hour at −78° C. 2,6-Dichloro-nicotinic acid (5.00 g, 26.0 mmol) was then added dropwise as a solution in THF (15 mL) and the reaction mixture was allowed to warm from −78° C. to room temperature and stir for 16 hours. The reaction mixture was quenched by the addition of H2O and the pH was adjusted to 0-2 with 6 N HCl and then diluted with EtOAc. The organic layer was separated and washed with H2O, saturated NaCl, dried (Na2SO4), and concentrated under reduced pressure. The crude product was triturated several times with ethyl acetate and the resulting solid was collected, washed with dichloromethane and dried under vacuum to yield 7.50 g (83%) pure desired product as a dark pink solid.

후처리

  1. temperatureto warm from −78° C. to room temperature
  2. stirringstir for 16 hours
  3. customThe reaction mixture was quenched by the addition of H2O
  4. additiondiluted with EtOAc
  5. customThe organic layer was separated
  6. washwashed with H2O, saturated NaCl
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was triturated several times with ethyl acetate
  10. customthe resulting solid was collected
  11. washwashed with dichloromethane
  12. customdried under vacuum

출처 및 근거

ORD 기록
ord-c97db87e6a554c07901967b0a77742cf
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732616B2

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