Trifluoroacetic acid → tert-butyl 5-((5-chloro-2-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

HRID 1478054Notes

Reaction equation

HRID 1478054 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:23][CH:12]3[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH:11]3[CH2:10]2)[C:5]([Cl:24])=[CH:4][N:3]=1.[CH:25]1([CH2:28][N:29]2[CH:33]=[C:32]([NH2:34])[CH:31]=[N:30]2)[CH2:27][CH2:26]1.FC(F)(F)C(O)=O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[Cl:24][C:5]1[C:6]([NH:8][CH:9]2[CH2:23][CH:12]3[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH:11]3[CH2:10]2)=[N:7][C:2]([NH:34][C:32]2[CH:31]=[N:30][N:29]([CH2:28][CH:25]3[CH2:27][CH2:26]3)[CH:33]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 435603721-(cyclopropylmethyl)-1H-pyrazol-4-amineHCID 118389983tert-butyl 5-((2,5-dichloropyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

Product 1

HCID 118390017tert-butyl 5-((5-chloro-2-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylateYield 271.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 5-[(2,5-dichloropyrimidin-4-yl)amino]-hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (1.10 g, 2.95 mmol) and 1-(cyclopropylmethyl)pyrazol-4-amine (38.5 mg, 0.28 mmol) in dioxane (10 mL) was added 2,2,2-trifluoroacetic acid (61.8 mg, 0.54 mmol). The reaction mixture was stirred at 100° C. overnight, then adjusted to pH=10 with a saturated Na2CO3 solution, and extracted with EtOAc (100 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 (EtOAc/PE (v/v)=1/2) to give the title compound as a pale yellow solid (0.36 g, 26%).

Workup

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

Sources & evidence

ORD record
ord-1f2793e397904b85890e60d1dc2da834
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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