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 1478040노트

반응식

HRID 1478040 반응식
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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-a4a5042616c74f8aa2f91b83287bade3
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403801B2

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