Diisopropylethylamine → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide

HRID 245988

반응식

HRID 245988 반응식
FC(F)(F)C(O)=O.[NH2:8][C@H:9]([CH3:18])[CH2:10][C:11]([N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:12].C(N(CC)C(C)C)(C)C.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:39]3[N:40]=[C:41]4[C:47]([C:48](O)=[O:49])=[CH:46][N:45]([CH2:51][O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])[C:42]4=[N:43][CH:44]=3)=[N:34][N:35]2[CH3:38])=[CH:31][CH:30]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:18][C@@H:9]([NH:8][C:48]([C:47]1[C:41]2[C:42](=[N:43][CH:44]=[C:39]([C:33]3[C:32]4[C:36](=[CH:37][C:29]([Cl:28])=[CH:30][CH:31]=4)[N:35]([CH3:38])[N:34]=3)[N:40]=2)[N:45]([CH2:51][O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])[CH:46]=1)=[O:49])[CH2:10][C:11](=[O:12])[N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1

참가 물질

6

반응물 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 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71280224(R)-3-amino-1-pyrrolidin-1-yl-butan-1-one trifluoroacetate

생성물 1

HCID 712861682-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide수율 96%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of (R)-3-amino-1-pyrrolidin-1-yl-butan-1-one trifluoroacetate (crude from step 2, 118 mg, 0.44 mmol) in DMF (2 mL) were added N,N-diisopropylethylamine (0.19 mL, 1.09 mmol), 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.22 mmol), and HATU (91 mg, 0.24 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (3×). 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% to 100% EtOAc/hexanes to afford 125 mg (96%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide as a white solid.

후처리

  1. customthen quenched with water
  2. extractionextracted with EtOAc (3×)
  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% to 100% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-8305e56bdb964af0bb69aadd29b4ce12
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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