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

HRID 1191238ノート

反応式

HRID 1191238 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e89ba6cd81a6486d80798099c6d6e104
出典データセット
uspto-grants-2014_03
特許番号
US08680098B2

反応ノート

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