Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 4,4-difluoro-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one

HRID 2364094ノート

反応式

HRID 2364094 の反応式
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][NH:10][C:11]=2[CH3:12])[S:4][C:3]=1[C:13]([NH2:15])=[O:14].[F:16][C:17]1([F:24])[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[F:16][C:17]1([F:24])[CH2:22][CH2:21][C:20]2([NH:1][C:2]3[CH:6]=[C:5]([C:7]4[CH:8]=[N:9][NH:10][C:11]=4[CH3:12])[S:4][C:3]=3[C:13](=[O:14])[NH:15]2)[CH2:19][CH2:18]1

参加物

7

反応物 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 157890924,4-DifluorocyclohexanoneHCID 667430133-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

生成物 1

HCID 667442354,4-difluoro-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one収率 39%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
80 °C

実験手順

A mixture of 3-amino-5-(5-methyl-1H-pyrazol-4-yl) thiophene-2-carboxamide (100 mg, 0.45 mmol), 4,4-difluorocyclohexanone (181 mg, 1.35 mmol), CSA (10 mg, 0.045 mmol), MgSO4 (108 mg, 0.90 mmol) and DMA (1 mL) was stirred at 80° C. for 2 h. The mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc to give the title compound (59 mg, 39%) as a pale yellow solid:

後処理

  1. extractionThe organic materials were extracted with EtOAc
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customAfter removal of the solvent at reduced pressure
  6. customthe residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc)
  7. customcrystallized from MeOH/EtOAc

出典と根拠

ORDレコード
ord-8469ed7e390d4222815ee5b85d582cdb
出典データセット
uspto-grants-2014_04
特許番号
US08691828B2

反応ノート

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