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 877137ノート

反応式

HRID 877137 の反応式
[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]

参加物

8

反応物 5

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

生成物 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)butanamide収率 59%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21226129Dichloromethane methanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-2c5d284733b24a6ebd84dd16b1ba45c4
出典データセット
uspto-grants-2015_03
特許番号
US08987298B2

反応ノート

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