Octahydropyrrolo(1,2-a)pyrazine → 5-(3,4,6,7,8,8a-Hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

HRID 16826

反応式

HRID 16826 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[NH:12][N:13]=[C:14]([O:16][CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=3)[CH:15]=2)=[O:9])=[N:6][CH:7]=1.[CH2:28]1[NH:33][CH2:32][CH2:31][N:30]2[CH2:34][CH2:35][CH2:36][CH:29]12>CS(C)=O>[CH2:28]1[CH:29]2[CH2:36][CH2:35][CH2:34][N:30]2[CH2:31][CH2:32][N:33]1[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[NH:12][N:13]=[C:14]([O:16][CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=3)[CH:15]=2)=[O:9])=[N:6][CH:7]=1

参加物

4

反応物 2

HCID 558578Octahydropyrrolo(1,2-a)pyrazineHCID 866210735-Chloro-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

生成物 1

HCID 665898625-(3,4,6,7,8,8a-Hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide収率 37.4%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
100 °C

実験手順

5-Chloro-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide (585 mg, 1.50 mmol) was added in one portion to 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine (379 mg, 3.00 mmol) in anhydrous dimethylsulfoxide (1.50 ml) at 25° C. The resulting solution was stirred at 100° C. for 18 h. The residue was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH to afford impure material. The concentrated eluent was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford impure product as a yellow solid. The impure material was then repurified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM. Pure fractions were evaporated to dryness to afford the title compound (269 mg, 37%) as a yellow solid.

後処理

  1. customThe residue was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customto afford impure material
  4. customThe concentrated eluent was purified by preparative HPLC
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness
  7. customto afford impure product as a yellow solid
  8. customThe impure material was then repurified by silica column chromatography
  9. washeluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM
  10. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-cbaed1bb1a61496bb30fc541ae73d34c
出典データセット
uspto-grants-2010_06
特許番号
US07737149B2

関連ノート

読み込み中…