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 1478040Notes

Reaction equation

HRID 1478040 reaction equation
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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-a4a5042616c74f8aa2f91b83287bade3
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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