Water → 8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-6-methyl-2-(2-trifluoromethyl-phenyl)-7H-purine trifluoroacetic acid salt

HRID 570255Notes

Reaction equation

HRID 570255 reaction equation
[NH2:1][C:2]1[C:3]([NH:19][C:20]([C:22]2[N:23]([CH3:31])[N:24]=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:26]=2)=O)=[N:4][C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:18])([F:17])[F:16])=[N:6][C:7]=1[CH3:8].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=[O:39].[OH2:47]>O1CCOCC1>[F:16][C:15]([F:18])([F:17])[C:10]([OH:39])=[O:47].[C:27]([C:25]1[CH:26]=[C:22]([C:20]2[NH:1][C:2]3[C:3](=[N:4][C:5]([C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[C:15]([F:18])([F:17])[F:16])=[N:6][C:7]=3[CH3:8])[N:19]=2)[N:23]([CH3:31])[N:24]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 962WaterHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 674110325-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [5-amino-6-methyl-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide

Product 1

HCID 1363374478-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-6-methyl-2-(2-trifluoromethyl-phenyl)-7H-purine trifluoroacetic acid salt

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [5-amino-6-methyl-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide (45.8 mg, 0.106 mmol, prepared as described in the previous step) in 1,4-dioxane (10 mL) was treated with CSA (49.2 mg, 0.213 mmol) and heated to 100° C. under a reflux condenser for 3 h. The cooled mixture was then diluted with water (20 mL) and extracted twice with EtOAc (25 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified by RP-HPLC on a C18 column eluting with a linear gradient of 10-80% CH3CN in 0.1% TFA/H2O over 25 min to 8-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-6-methyl-2-(2-trifluoromethyl-phenyl)-7H-purine trifluoroacetic acid salt as an off-white solid. 1H-NMR (400 MHz, CD3OD) δ: 7.77 (d, J=7.6 Hz, 1H), 7.57-7.70 (m, 3H), 6.87 (s, 1H), 4.27 (s, 3H), 2.80 (s, 3H), 1.28 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H21F3N6: 415.2 (M+H); Measured: 415.2.

Workup

  1. extractionextracted twice with EtOAc (25 mL)
  2. dry with materialThe combined extracts were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by RP-HPLC on a C18 column
  5. washeluting with a linear gradient of 10-80% CH3CN in 0.1% TFA/H2O over 25 min to 8-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-6-methyl-2-(2-trifluoromethyl-phenyl)-7H-purine trifluoroacetic acid salt as an off-white solid

Sources & evidence

ORD record
ord-d30557fb5df443a1bf6c29ea5a22b58b
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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