Sodium Hydroxide → N-(3-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79398

反応式

HRID 79398 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]3[C:17]([C:20]([O-:22])=O)=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH2:4][CH2:3]1.[Li+].ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH:36]1([C:39]2[C:47]3[C:46]([NH2:48])=[CH:45][CH:44]=[CH:43][C:42]=3[N:41]([CH2:49][C:50]3[CH:54]=[CH:53][N:52]([CH:55]([CH3:57])[CH3:56])[N:51]=3)[N:40]=2)[CH2:38][CH2:37]1.[OH-].[Na+]>CN1C(=O)CCC1>[CH:36]1([C:39]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][C:46]=3[NH:48][C:20]([C:17]3[N:14]4[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)=[CH:12][C:13]4=[N:19][CH:18]=3)=[O:22])[N:41]([CH2:49][C:50]3[CH:54]=[CH:53][N:52]([CH:55]([CH3:57])[CH3:56])[N:51]=3)[N:40]=2)[CH2:37][CH2:38]1

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 67252742Lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672610713-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine

生成物 1

HCID 67261540N-(3-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide収率 70.5%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
0 °C

実験手順

To lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (130 mg, 0.411 mmol) was added NMP (10 mL). The solution was cooled to 0° C. and 2,4,6-trichlorobenzoyl chloride (65.6 μl, 0.411 mmol) was added dropwise. The cold bath was removed once the addition was complete. The reaction mixture was stirred for 1 hour during which time a cloudy suspension formed. 3-Cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine (90 mg, 0.305 mmol) was added and the reaction mixture was heated at 88° C. for 11 hours. The mixture was cooled to ambient temperature and NMP was removed by vacuum distillation to give an oily residue. To this was added 10% NaOH aqueous solution (10 mL) and the resulting clear solution was stirred at 80° C. for 30 minutes. The solution was cooled to ambient temperature and extracted with DCM. The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure and the residue was triturated with Et2O (50 mL). The resulting solids were collected by filtration, washed with Et2O (40 mL) and dried under vacuum to give the final product (125 mg). MS (ES+APCI) m/z=582 (M+H).

後処理

  1. customThe cold bath was removed once the addition
  2. customformed
  3. temperaturethe reaction mixture was heated at 88° C. for 11 hours
  4. temperatureThe mixture was cooled to ambient temperature
  5. customNMP was removed by vacuum distillation
  6. customto give an oily residue
  7. stirringthe resulting clear solution was stirred at 80° C. for 30 minutes
  8. temperatureThe solution was cooled to ambient temperature
  9. extractionextracted with DCM
  10. dry with materialThe combined organic extracts were dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customthe residue was triturated with Et2O (50 mL)
  13. filtrationThe resulting solids were collected by filtration
  14. washwashed with Et2O (40 mL)
  15. customdried under vacuum

出典と根拠

ORDレコード
ord-5e83680aa6b14f12ad7ecadeaecee382
出典データセット
uspto-grants-2014_09
特許番号
US08841455B2

関連ノート

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