Dimethylformamide → Selonsertib

HRID 402584ノート

反応式

HRID 402584 の反応式
Cl.[CH:2]1([C:5]2[N:6]=[CH:7][N:8]([C:10]3[C:11]([CH3:20])=[CH:12][C:13]([F:19])=[C:14]([CH:18]=3)[C:15]([OH:17])=O)[CH:9]=2)[CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[CH:32]([N:35]1[CH:39]=[N:38][N:37]=[C:36]1[C:40]1[N:45]=[C:44]([NH2:46])[CH:43]=[CH:42][CH:41]=1)([CH3:34])[CH3:33].C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1>[CH:2]1([C:5]2[N:6]=[CH:7][N:8]([C:10]3[C:11]([CH3:20])=[CH:12][C:13]([F:19])=[C:14]([CH:18]=3)[C:15]([NH:46][C:44]3[CH:43]=[CH:42][CH:41]=[C:40]([C:36]4[N:35]([CH:32]([CH3:34])[CH3:33])[CH:39]=[N:38][N:37]=4)[N:45]=3)=[O:17])[CH:9]=2)[CH2:3][CH2:4]1

参加物

7

反応物 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 815728386-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-amine2 回HCID 866912505-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzoic acid hydrochloride

生成物 1

HCID 71245288Selonsertib

試薬・触媒・溶媒 1

HCID 142844-(Dimethylamino)pyridine触媒

実験手順

5-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzoic acid hydrochloride (1.5 g, 5.07 mmol) was suspended in anhydrous 1,2-dichloromethane (25 mL) at room temperature. Oxalyl chloride (0.575 ml, 6.59 mmol) was added with stirring under nitrogen, followed by N,N-dimethylformamide (0.044 ml, 0.507 mmol). The mixture was stirred for 4 hr at room temperature, and then the solvent was removed under reduced pressure. The residue was dissolved in 25 mL anhydrous dichloromethane. 6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-amine (1.13 g, 5.58 mmol) (compound C) and 4-dimethylaminopyridine (0.62 g, 5.07 mmol) were rapidly added with stirring under nitrogen. The reaction was stirred for 2 hours at room temperature and aqueous saturated NaHCO3 (15 mL) was added. The mixture was stirred for 10 minutes, and the layers were separated, and the aqueous layer was washed 1×20 mL dichloromethane. The combined organics were dried (MgSO4), filtered and concentrated. The residue was dissolved in a minimum amount of CH3CN and water was slowly added until solids precipitated from the mixture. The solid was collected by filtration and dried to give 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide in ˜96% purity (1.28 g, 2.88 mmol). Anal. LC/MS (m/z: 446, M+1). The material was further purified by RP-HPLC (reverse phase HPLC) to obtain an analytically pure sample as the HCl salt.

後処理

  1. stirringThe mixture was stirred for 4 hr at room temperature
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in 25 mL anhydrous dichloromethane
  4. stirringwith stirring under nitrogen
  5. stirringThe reaction was stirred for 2 hours at room temperature
  6. stirringThe mixture was stirred for 10 minutes
  7. customthe layers were separated
  8. washthe aqueous layer was washed 1×20 mL dichloromethane
  9. dry with materialThe combined organics were dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in a minimum amount of CH3CN and water
  13. additionwas slowly added until solids
  14. customprecipitated from the mixture
  15. filtrationThe solid was collected by filtration
  16. customdried

出典と根拠

ORDレコード
ord-447bae7201dc42449447a830986d1f04
出典データセット
uspto-grants-2014_06
特許番号
US08742126B2

反応ノート

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