Lithium Chloride → Methyl 4-(2-ethoxyvinyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate

HRID 640698노트

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HRID 640698 반응식
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:24]([O:26][CH3:27])=[O:25])[C:15](OS(C(F)(F)F)(=O)=O)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[Cl-].[Li+].[CH2:32]([O:34][CH:35]=[CH:36][Sn](CCCC)(CCCC)CCCC)[CH3:33]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:35]([O:34][CH:32]=[CH:33][C:15]1[C:14]([C:24]([O:26][CH3:27])=[O:25])=[N:13][CH:12]=[C:11]2[N:7]([CH2:6][C:5]3[CH:28]=[CH:29][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=[CH:9][C:10]=12)[CH3:36]

참가 물질

6

반응물 3

HCID 433294Lithium ChlorideHCID 2763294(Z)-1-Ethoxy-2-(tributylstannyl)etheneHCID 532374681h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-4-[[(trifluoromethyl)sulfonyl]oxy]-,methyl ester

생성물 1

HCID 68665270Methyl 4-(2-ethoxyvinyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate수율 89.2%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매2회

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온도
79 °C

실험 절차

To a solution of methyl 1-(4-fluorobenzyl)-4-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (2 g, 4.62 mmol) in DMF (27 mL) was added lithium chloride (0.59 mg, 13.88 mmol). Dry nitrogen was bubbled through the mixture for for 10 min, and then dichlorobis(triphenylphosphine)palladium(II) (0.16 g, 0.23 mmol) was added. The mixture was heated to 79° C., and a solution of ethoxyvinyl tributyltin (mixture of isomers: 1,2-E:1,2-Z:1,1=1:0: 0.97:0.18) [prepared according to A. Leusik, H. A. Budding, J. W. Marsman, J. Organomet. Chem., 1967, 9, 285-294] (1.82 g, 5.08 mmol) in DMF (23 mL). The resulting mixture was stirred for 9 h at 70° C. under nitrogen atmosphere. It was quenched with saturated sodium chloride and filtered to remove solid precipitate then concentrated. Purification by flash chromatography (Biotage) over silica gel (1:1 to 1:3, hexane/ethyl acetate) afforded the title product as brown glue (1.46 g, 89.2% yield). LCMS (APCl, M+H+): 355.2.

후처리

  1. customDry nitrogen was bubbled through the mixture for for 10 min
  2. customIt was quenched with saturated sodium chloride
  3. filtrationfiltered
  4. customto remove solid precipitate
  5. concentrationthen concentrated
  6. customPurification by flash chromatography (Biotage) over silica gel (1:1 to 1:3, hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-3f6e3e12e082489a96a0d48f20c487f0
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07692014B2

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