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Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide

HRID 245929
ノート
印刷プレビュー

反応式

HRID 245929 の反応式
C(N(CC)C(C)C)(C)C.[F:10][C:11]1[CH:19]=[C:18]2[C:14]([C:15]([C:21]3[N:22]=[C:23]4[C:29]([C:30]([OH:32])=O)=[CH:28][N:27]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:24]4=[N:25][CH:26]=3)=[N:16][N:17]2[CH3:20])=[CH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[NH2:72][C@H:73]([CH3:80])[C:74]([NH:76][CH2:77][CH2:78][OH:79])=[O:75]>CN(C=O)C>[OH:79][CH2:78][CH2:77][NH:76][C:74]([C@H:73]([NH:72][C:30]([C:29]1[C:23]2[C:24](=[N:25][CH:26]=[C:21]([C:15]3[C:14]4[C:18](=[CH:19][C:11]([F:10])=[CH:12][CH:13]=4)[N:17]([CH3:20])[N:16]=3)[N:22]=2)[N:27]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:39])([CH3:38])[CH3:40])[CH:28]=1)=[O:32])[CH3:80])=[O:75]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 86677924HCID 86677924、化合物

生成物 1

HCID 71288187
2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide
収率 59%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

In a round-bottomed flask, (R)-2-amino-N-(2-hydroxy-ethyl)-propionamide trifluoroacetate (crude from Step 2) was dissolved in DMF (2 ml) and N,N-diisopropylethylamine (0.70 ml, 4.0 mmol) was added. Then 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (170 mg, 0.39 mmol) was added followed by HATU (161 mg, 0.42 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and diluted with petroleum ether. The resulting suspension was filtered. The filter cake was washed with water and petroleum ether then dried under high vacuum. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc) and MeOH/EtOAc (gradient 0-10% MeOH) to give 127 mg (59%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide as an off-white solid.

後処理

  1. customthen quenched with water
  2. additiondiluted with petroleum ether
  3. filtrationThe resulting suspension was filtered
  4. washThe filter cake was washed with water and petroleum ether
  5. customthen dried under high vacuum
  6. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc) and MeOH/EtOAc (gradient 0-10% MeOH)

出典と根拠

ORDレコード
ord-647c7a0b705d4da49e7e33a9df85b8cd
出典データセット
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08658646B2

反応ノート

読み込み中…

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