1-Hydroxybenzotriazole → (2E)-3-[5-({(3R)-1-[2-(dimethylamino)benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 2354090ノート

反応式

HRID 2354090 の反応式
[CH3:1][N:2]([CH3:27])[C:3]1[CH:26]=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C@@H:8]([NH:11][C:12]2[N:13]=[CH:14][C:15](/[CH:18]=[CH:19]/[C:20](O)=[O:21])=[N:16][CH:17]=2)[CH2:7]1.[O:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH:29]1[O:34][NH2:35].C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:27][N:2]([CH3:1])[C:3]1[CH:26]=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C@@H:8]([NH:11][C:12]2[N:13]=[CH:14][C:15](/[CH:18]=[CH:19]/[C:20]([NH:35][O:34][CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33][O:28]3)=[O:21])=[N:16][CH:17]=2)[CH2:7]1

参加物

6

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67128945(2E)-3-[5-({(3R)-1-[2-(dimethylamino) benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]acrylic acid

生成物 1

HCID 86628129(2E)-3-[5-({(3R)-1-[2-(dimethylamino)benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide収率 49.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of crude (2E)-3-[5-({(3R)-1-[2-(dimethylamino) benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]acrylic acid (311 mg), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (108 mg), and HOBT (125 mg) in DMF (2.4 mL) was added WSCD (164 uL), which was stirred at room temperature for 17 hours. To the resultant was added saturated NaHCO3 aq. The mixture was extracted with AcOEt. The organic phase was washed with brine, dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give (2E)-3-[5-({(3R)-1-[2-(dimethylamino)benzyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (195 mg) as a yellow amorphous.

後処理

  1. additionwas added WSCD (164 uL), which
  2. extractionwas extracted with AcOEt
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography on silica gel

出典と根拠

ORDレコード
ord-a6a98da1722d4d7c83a472a789ad68b1
出典データセット
uspto-grants-2010_07
特許番号
US07750155B2

反応ノート

読み込み中…