Ammonium Hydroxide → N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-2-nitro-4-piperidin-1-ylmethyl-benzamide

HRID 512966

反応式

HRID 512966 の反応式
Cl.[N+:2]([C:5]1[CH:13]=[C:12]([CH2:14][N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)([O-:4])=[O:3].S(Cl)(Cl)=O.[F:25][C:26]1[CH:27]=[C:28]([CH:40]=[C:41]([F:43])[CH:42]=1)[CH2:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][N:34]=[C:33]2[NH2:39].[NH4+].[OH-]>N1C=CC=CC=1.O.CCOC(C)=O>[F:25][C:26]1[CH:27]=[C:28]([CH:40]=[C:41]([F:43])[CH:42]=1)[CH2:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[NH:35][N:34]=[C:33]2[NH:39][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:12]([CH2:14][N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:13][C:5]=1[N+:2]([O-:4])=[O:3]

参加物

8

反応物 4

HCID 14923Ammonium HydroxideHCID 24386Thionyl ChlorideHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amineHCID 686710012-Nitro-4-piperidin-1-ylmethyl-benzoic acid hydrochloride

生成物 1

HCID 68672122N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-2-nitro-4-piperidin-1-ylmethyl-benzamide収率 43.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1049Pyridine溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
4 °C

実験手順

2-Nitro-4-piperidin-1-ylmethyl-benzoic acid hydrochloride (440 mg, 1.46 mmol) was treated with thionyl chloride (5 mL) and refluxed for 1 hour. Excess of reagent was removed by evaporation followed by evaporation from toluene (2×5 mL). The solid was further died under vacuum. The acid chloride was treated with dry pyridine (7 mL), cooled to 4° C. and added with 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (315 mg, 1.22 mmol) in dry pyridine (3 mL) under a nitrogen atmosphere, with stirring. After stirring for a few hours the reaction was left at 0° C. over-night. EtOAc (50 mL) and water (50 mL) were added, pH was adjusted to 9 with concentrated NH4OH. The organic layer was separated, dried over sodium sulphate, evaporated to dryness and purified over silica gel (DCM: MeOH 95:5) affording 266 mg of title compound in 43% yield.

後処理

  1. temperaturerefluxed for 1 hour
  2. customExcess of reagent was removed by evaporation
  3. customfollowed by evaporation from toluene (2×5 mL)
  4. additionThe acid chloride was treated with dry pyridine (7 mL)
  5. stirringAfter stirring for a few hours the reaction
  6. waitwas left at 0° C. over-night
  7. customThe organic layer was separated
  8. dry with materialdried over sodium sulphate
  9. customevaporated to dryness
  10. custompurified over silica gel (DCM: MeOH 95:5)

出典と根拠

ORDレコード
ord-f2f079675df04cee982f5c2b87562aa1
出典データセット
uspto-grants-2015_08
特許番号
US09102662B2

関連ノート

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