Hydrochloric Acid → 5-methyl-N2-(1-methyl-1H-pyrazol-4-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine

HRID 1478029Notes

Reaction equation

HRID 1478029 reaction equation
[CH3:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:33][CH2:32][C:19]3([CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)[CH2:18][CH2:17]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)=[N:6][CH:7]=1.Cl.CCOC(C)=O>C(Cl)Cl>[CH3:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:33][CH2:32][C:19]3([CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[CH2:18][CH2:17]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 118390020tert-butyl 9-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 1183900055-methyl-N2-(1-methyl-1H-pyrazol-4-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamineYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 9-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecane-3-carboxylate (400 mg, 0.88 mmol) in DCM (20 mL) was added a solution of HCl in EtOAc (20 mL, 80 mmol). The reaction mixture was stirred at rt overnight and concentrated in vacuo. The residue was dissolved in water (50 mL) and adjusted to pH=10 with a saturated Na2CO3 aqueous solution, then extracted with DCM (200 mL×3). The combined organic phases were washed with brine (200 mL), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (a solution of NH3 in MeOH (7 M)/MeOH/DCM (v/v/v)=1/20/60) to give the title compound as a beige solid (100.2 mg, 32%).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in water (50 mL)
  3. extractionextracted with DCM (200 mL×3)
  4. washThe combined organic phases were washed with brine (200 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography (a solution of NH3 in MeOH (7 M)/MeOH/DCM (v/v/v)=1/20/60)

Sources & evidence

ORD record
ord-a2d94b6e943d40deba4c173ac1ca1ccf
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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