Isopropylamine → 2-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246080ノート

反応式

HRID 246080 の反応式
[CH:1]([N:14]1[CH2:17][CH:16]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=3)[C:20]([C:28]3[N:29]=[C:30]4[C:36]([C:37](O)=[O:38])=[CH:35][N:34]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[C:31]4=[N:32][CH:33]=3)=[N:19]2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=[N:63][C:58]2[CH:59]=CC=N[C:57]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N)(C)C>CN(C=O)C>[CH:58]([NH:63][C:37]([C:36]1[C:30]2[C:31](=[N:32][CH:33]=[C:28]([C:20]3[C:21]4[C:26](=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[N:18]([CH:16]4[CH2:17][N:14]([CH:1]([C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=5)[CH2:15]4)[N:19]=3)[N:29]=2)[N:34]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:46])([CH3:47])[CH3:45])[CH:35]=1)=[O:38])([CH3:59])[CH3:57]

参加物

5

反応物 3

HCID 6363IsopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712798582-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 712793702-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide収率 54%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (130 mg, 0.20 mmol) in DMF (2 mL) were added HATU (84 mg, 0.22 mmol) and isopropylamine (86 μL, 1.00 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (2×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% EtOAc/hexanes to isolate 74 mg (54%) of 2-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as an off-white foamy solid.

後処理

  1. customthen quenched with water
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organics were washed with water (3×) and brine
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography with 50% EtOAc/hexanes

出典と根拠

ORDレコード
ord-d1918548e73a403f81b7c9a9fea793d6
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…