Trifluoroacetic acid → 3-methyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide

HRID 877137노트

반응식

HRID 877137 반응식
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:24])[CH2:20][CH:21]([CH3:23])[CH3:22])[CH:15]=[N:16][CH:17]=3)[CH:10]=2)[N:5](C2CCCCO2)[N:4]=1)=O.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([C:38]2[C:39]([NH2:45])=[C:40]([NH2:44])[CH:41]=[N:42][CH:43]=2)[CH2:34][CH2:33]1.[S].[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>CN(C=O)C.CO.C(Cl)Cl>[CH3:22][CH:21]([CH3:23])[CH2:20][C:19]([NH:18][C:14]1[CH:15]=[N:16][CH:17]=[C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[NH:5][N:4]=[C:3]3[C:1]2[NH:44][C:40]3[CH:41]=[N:42][CH:43]=[C:38]([N:35]4[CH2:34][CH2:33][N:32]([CH3:31])[CH2:37][CH2:36]4)[C:39]=3[N:45]=2)[CH:13]=1)=[O:24]

참가 물질

8

반응물 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 5362487SulfurHCID 583776555-(4-Methylpiperazin-1-yl)pyridine-3,4-diamineHCID 86698333HCID 86698333, 화합물

생성물 1

HCID 1362730783-methyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide수율 59%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 21226129Dichloromethane methanol용매

실험 절차

A solution of N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide (LXXXIV) (52 mg, 0.127 mmol), 5-(4-methylpiperazin-1-yl)pyridine-3,4-diamine (LVIII) (29 mg, 0.13 mmol) and sulfur (45 mg, 0.13 mmol) in dry DMF (10 mL) was heated at 140° C. overnight. The reaction was cooled and evaporated under vacuum. The viscous residue was dried overnight under vacuum. The solid was washed with cold water and dried under vacuum. The crude product (L V) was dissolved in DCM (5 mL) followed by Et3SiH (48 μL, 0.30 mmol) and slowly addition of TFA (2.5 mL) The reaction was stirred until TLC (10% MeOH/DCM) showed the reaction was complete. The reaction was evaporated under vacuum and the residue was treated with water, sonicated and then basified with aq. ammonia. The solids were filtered, washed with cold water and dried. The crude product was heated in EtOAc and filtered hot to remove impurities. The hot EtOAc solution was allowed to slowly cool to room temperature and filtered to give 3-methyl-N-(5-(3-(7-(4-methylpiperazin-1-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)butanamide 1 as a pink solid (36 mg, 0.071 mmol, 59% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 0.97 (d, 6H), 2.13 (m, 1H), 2.27 (m, 4H), 3.45 (m, 4H), 6.70 (s, 1H), 7.79 (dd, 2H), 8.36 (s, 1H), 8.62 (s, 1H), 8.65 (s, 1H), 8.66 (s, 1H), 8.84 (s, 1H), 10.26 (s, 1H), 12.97 (s, 1H), 13.82 (s, 1H); ESIMS found for C28H31N9O m/z 510.5 (M+H).

후처리

  1. temperatureThe reaction was cooled
  2. customevaporated under vacuum
  3. customThe viscous residue was dried overnight under vacuum
  4. washThe solid was washed with cold water
  5. customdried under vacuum
  6. dissolutionThe crude product (L V) was dissolved in DCM (5 mL)
  7. customThe reaction was evaporated under vacuum
  8. additionthe residue was treated with water
  9. customsonicated
  10. filtrationThe solids were filtered
  11. washwashed with cold water
  12. customdried
  13. temperatureThe crude product was heated in EtOAc
  14. filtrationfiltered hot
  15. customto remove impurities
  16. filtrationfiltered

출처 및 근거

ORD 기록
ord-2c5d284733b24a6ebd84dd16b1ba45c4
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987298B2

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