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 246080노트

반응식

HRID 246080 반응식
[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]

참가 물질

5

반응물 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

생성물 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 isopropylamide수율 54%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d1918548e73a403f81b7c9a9fea793d6
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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