Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide

HRID 246558

反応式

HRID 246558 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Cl.[CH3:33][O:34][NH2:35].C(N(C(C)C)CC)(C)C.C1CN(C(ON2N=NC3C2=CC=CC=3)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[CH3:33][O:34][NH:35][C:21]([C:20]1[C:14]2[C:15](=[N:16][CH:17]=[C:12]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH3:11])[N:7]=3)[N:13]=2)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:19]=1)=[O:23]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 13685355O-(Benzotriazol-1-yl)-N,N,N',N'-bis(tetramethylene)uronium HexafluorophosphateHCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 866779872-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide収率 99.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred suspension of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (50 mg, 113 μmol) and O-methylhydroxylamine hydrochloride (11.3 mg, 136 μmol) and diisopropylethylamine (79 μL, 453 μmol) in DMF (2 mL) was added o-(benzotriazol-1-yl)-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate (58.6 mg, 136 μmol) at 20° C. for overnight. The reaction mixture was diluted with ethyl acetate and washed with 1 N HCl solution. The organic layer was then washed with saturated sodium bicarbonate and brine then dried (sodium sulfate), filtered and concentrated in vacuo to give the crude 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide (53 mg) as a white solid. This was used directly in the next step without further purification. MS (M+H)+=471.

後処理

  1. washwashed with 1 N HCl solution
  2. washThe organic layer was then washed with saturated sodium bicarbonate and brine
  3. dry with materialthen dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-4ad6686c5b594e008a76eb3914676497
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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