Trifluoroacetic acid → 5-chloro-N2-(1,5-dimethyl-1H-pyrazol-3-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine

HRID 1478040ノート

反応式

HRID 1478040 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:26][CH2:25][C:12]3([CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]3)[CH2:11][CH2:10]2)[C:5]([Cl:27])=[CH:4][N:3]=1.[CH3:28][N:29]1[C:33]([CH3:34])=[CH:32][C:31]([NH2:35])=[N:30]1.FC(F)(F)C(O)=O>O1CCOCC1>[Cl:27][C:5]1[C:6]([NH:8][CH:9]2[CH2:10][CH2:11][C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:25][CH2:26]2)=[N:7][C:2]([NH:35][C:31]2[CH:32]=[C:33]([CH3:34])[N:29]([CH3:28])[N:30]=2)=[N:3][CH:4]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 70177471,5-dimethyl-1H-pyrazol-3-amineHCID 118390013Tert-butyl 3-[(2,5-dichloropyrimidin-4-yl)amino]-9-azaspiro[5.5]undecane-9-carboxylate

生成物 1

HCID 1183900765-chloro-N2-(1,5-dimethyl-1H-pyrazol-3-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine収率 95.3%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of tert-butyl 9-((2,5-dichloropyrimidin-4-yl)amino)-3-azaspiro[5.5]undecane-3-carboxylate (1.52 g, 3.66 mmol) and 1,5-dimethyl-1H-pyrazol-3-amine (800.0 mg, 7.198 mmol in 1,4-dioxane (20 mL) was added trifluoroacetic acid (2.1 g, 18 mmol). The mixture was stirred at 100° C. overnight and concentrated in vacuo. The residue was dissolved in methanol (5 mL), and adjust to Ph=8˜9 with the saturated aqueous solution of NaHCO3. Then the mixture was exacted with DCM/MeOH (50 mL/10 mL) and the separated organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash silica gel column chromatography (DCM/MeOH (v/v)=50/1 to 10/1) to give the product as a yellow white solid (1.36 g, 95.3%).

後処理

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in methanol (5 mL)
  3. washthe separated organic layer was washed with brine (100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash silica gel column chromatography (DCM/MeOH (v/v)=50/1 to 10/1)

出典と根拠

ORDレコード
ord-a4a5042616c74f8aa2f91b83287bade3
出典データセット
uspto-grants-2016_08
特許番号
US09403801B2

反応ノート

読み込み中…