Potassium Hydroxide → Allyl 2-amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 869112Notes

Reaction equation

HRID 869112 reaction equation
O1CCO[CH:2]1[CH2:6][C:7](=O)[C:8]([F:11])([F:10])[F:9].[NH2:13][C:14]1[C:18]([C:19]([O:21][CH2:22][CH:23]=[CH2:24])=[O:20])=[C:17]([NH2:25])[NH:16][N:15]=1.[OH-].[K+]>O1CCOCC1>[NH2:25][C:17]1[C:18]([C:19]([O:21][CH2:22][CH:23]=[CH2:24])=[O:20])=[C:14]2[N:13]=[C:7]([C:8]([F:9])([F:10])[F:11])[CH:6]=[CH:2][N:15]2[N:16]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 552960491-(1,3-Dioxolane-2-yl)-3,3,3-trifluoropropane-2-oneHCID 73554792Allyl 3,5-diamino-1H-pyrazole-4-carboxylate

Product 1

HCID 90417814Allyl 2-amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-(1,3-Dioxolan-2-yl)-1,1,1-trifluoro-propan-2-one (55.58 g, 301.9 mmol) and allyl 3,5-diamino-1H-pyrazole-4-carboxylate 3 (55 g, 301.9 mmol) were dissolved in 1,4-dioxane (330 mL). KOH (1.694 g, 30.19 mmol) was added and the yellow suspension was stirred at room temperature for 4 h30 min. The reaction mixture was heated at 90° C. for 16 h. The mixture was cooled down to room temperature. The reaction mixture was concentrated and purified by column chromatography (CombiFlash Companion XL, 1.5 kg column, 0.5 to 40% EtOAc in DCM) to afford allyl 2-amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate 4a as a bright yellow solid (68 g, 79% yield). LC-MS (M+H)+ 287.2; 1H NMR (500 MHz, DMSO-d6) δ 9.18 (m, 1H), 7.46 (m, 1H), 6.77 (s, 2H), 6.05 (m, 1H), 5.62 (m, 1H), 5.26 (m, 1H), 4.78 (m, 2H).

Workup

  1. temperatureThe reaction mixture was heated at 90° C. for 16 h
  2. temperatureThe mixture was cooled down to room temperature
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by column chromatography (CombiFlash Companion XL, 1.5 kg column, 0.5 to 40% EtOAc in DCM)

Sources & evidence

ORD record
ord-d14bbb6ea2d04d9a810f45155cecfcb4
Source dataset
uspto-grants-2015_03
Patent number
US08969360B2

Reaction notes

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