Dimethylformamide → Selonsertib

HRID 402584노트

반응식

HRID 402584 반응식
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

참가 물질

7

반응물 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 815728386-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-amine2회HCID 866912505-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzoic acid hydrochloride

생성물 1

HCID 71245288Selonsertib

시약·촉매·용매 1

HCID 142844-(Dimethylamino)pyridine촉매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-447bae7201dc42449447a830986d1f04
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08742126B2

반응 노트

불러오는 중…