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

HRID 1478072Notes

Reaction equation

HRID 1478072 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.Cl.[CH3:29][N:30]1[CH:34]=[C:33]([NH2:35])[C:32]([CH3:36])=[N:31]1.FC(F)(F)C(O)=O>CCCCO>[Cl:27][C:5]1[C:6]([NH:8][CH:9]2[CH2:26][CH2:25][C:12]3([CH2:13][CH2:14][NH:15][CH2:16][CH2:17]3)[CH2:11][CH2:10]2)=[N:7][C:2]([NH:35][C:33]2[C:32]([CH3:36])=[N:31][N:30]([CH3:29])[CH:34]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 126871971,3-dimethyl-1H-pyrazol-4-amine hydrochlorideHCID 118390013HCID 118390013, compound

Product 1

HCID 1183900335-chloro-N2-(1,3-dimethyl-1H-pyrazol-4-yl)-N4-(3-azaspiro[5.5]undecan-9-yl) pyrimidine-2,4-diamineYield 57.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

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 (504.1 mg, 1.214 mmol) and 1,3-dimethyl-1H-pyrazol-4-amine hydrochloride (381.0 mg, 2.581 mmol) in n-BuOH (10 mL) was added trifluoroacetic acid (678.1 mg, 5.947 mmol). The mixture was stirred at 100° C. overnight, then quenched with water (30 mL), and adjusted to pH=9 with solid NaHCO3, and then extracted with DCM (200 mL×3). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/10) to give the title compound as brown oil (271 mg, 45.57%).

Workup

  1. customquenched with water (30 mL)
  2. extractionextracted with DCM (200 mL×3)
  3. washThe combined organic phases were washed with brine (100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/10)

Sources & evidence

ORD record
ord-03bce45b7eff44b7b62e2d378d76b028
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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