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

HRID 15944

反応式

HRID 15944 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c97db87e6a554c07901967b0a77742cf
出典データセット
uspto-grants-2010_06
特許番号
US07732616B2

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