Hydrochloric Acid → 1-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(pyridin-4-yl)-1H-isoindol-3-amine

HRID 1662177ノート

反応式

HRID 1662177 の反応式
I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C([Li])(C)(C)C.[Br:13][C:14]1[CH:15]=[C:16]([C:21]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:30]=2[C:36]#[N:37])=[N:22]S(C(C)(C)C)=O)[CH:17]=[CH:18][C:19]=1[F:20].Cl>C1COCC1>[Br:13][C:14]1[CH:15]=[C:16]([C:21]2([C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[C:29]3[C:30](=[C:31]([F:35])[CH:32]=[CH:33][CH:34]=3)[C:36]([NH2:37])=[N:22]2)[CH:17]=[CH:18][C:19]=1[F:20]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 6094924-IodopyridineHCID 76821603N-((3-Bromo-4-fluorophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178418306HCID 178418306、化合物

生成物 1

HCID 585794771-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(pyridin-4-yl)-1H-isoindol-3-amine収率 9.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-100 °C

実験手順

A solution of 4-iodopyridine (0.530 g, 2.59 mmol) in THF (5 mL) was added dropwise to a is mixture of tert-butyllithium (1.6 M in pentane, 2.94 mL, 4.70 mmol) in THF (20.00 mL) at −100° C. under an argon atmosphere. N-((3-Bromo-4-fluorophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (1.00 g, 2.35 mmol) in THF (7.50 mL) was added and the resulting reaction mixture was stirred at −100° C. for 30 min. The cooling bath was removed and the mixture was stirred at room temperature for 2 h. Water was added and the mixture was extracted with EtOAc (×3). The combined organic layers were dried over Na2SO4 and concentrated. The residue was dissolved in MeOH (15.00 mL), and then hydrogen chloride (2 M in diethyl ether, 2.351 mL, 4.70 mmol) was added and the mixture was stirred at room temperature for 1.5 h. The solvents were removed in vacuo, and the residue was partitioned between aqueous sodium bicarbonate (saturated) and chloroform. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel chromatography using a gradient of 0 to 10% (3.5 M ammonia in methanol) in dichloromethane afforded 0.088 g (9% yield) of the title compound. MS (ES+) m/z 400 [M+1]+.

後処理

  1. customthe resulting reaction mixture
  2. customThe cooling bath was removed
  3. stirringthe mixture was stirred at room temperature for 2 h
  4. additionWater was added
  5. extractionthe mixture was extracted with EtOAc (×3)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in MeOH (15.00 mL)
  9. stirringthe mixture was stirred at room temperature for 1.5 h
  10. customThe solvents were removed in vacuo
  11. customthe residue was partitioned between aqueous sodium bicarbonate (saturated) and chloroform
  12. dry with materialThe combined organic layers were dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customPurification by silica gel chromatography

出典と根拠

ORDレコード
ord-f698187867bd442cae07cbe01d31ef25
出典データセット
uspto-grants-2011_10
特許番号
US08030500B2

反応ノート

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