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Lithium hexamethyldisilazane → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,2,3-dibromo-1-[(4-fluorophenyl)methyl]-4-hydroxy-,ethyl ester

HRID 2377079
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HRID 2377079 반응식
[Br:1][C:2]1[C:3]([C:34]([O:36]CC)=O)=[C:4]([CH2:16][N:17]([CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])S(C2C=CC(C)=CC=2)(=O)=O)[N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[C:6]=1[Br:7].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:7][C:6]1[N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[C:4]2=[CH:16][N:17]=[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:34]([OH:36])=[C:3]2[C:2]=1[Br:1]
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반응물 2

HCID 2733832Lithium hexamethyldisilazaneHCID 59855815Ethyl 4,5-dibromo-1-(4-fluorobenzyl)-2-({(2-ethoxy-2-oxoethyl)[(4-methylphenyl)sulfonyl]amino}methyl)-1H-pyrrole-3-carboxylate

생성물 1

HCID 598558191h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,2,3-dibromo-1-[(4-fluorophenyl)methyl]-4-hydroxy-,ethyl ester수율 60%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a stirring solution of ethyl 4,5-dibromo-1-(4-fluorobenzyl)-2-({(2-ethoxy-2-oxoethyl)[(4-methylphenyl) sulfonyl]amino}methyl)-1H-pyrrole-3-carboxylate (124.2 g, 184.3 mol) in anhydrous THF (1.0 L) was added LiHMDS (405 mL, 1.0M in THF, 0.405 mol) at −78° C. over 1 h. The mixture was quenched with aq. NH4Cl, extracted with ethyl acetate. The organic layer was dried over Na2SO4, and concentrated. The residue was purified by column chromatography with etyl acetate/hexane (1/1, v:v) to ethyl acetate/dichloromethane (9/1) to give the title product (52.0 g 60% yield). 1H NMR (DMSO-d6) δ ppm. 11.50 (s, 1H), 8.63 (s, 1H), 7.16 (d, J=7.2 Hz, 4H), 5.60 (s, 2H), 5.67 (s, 2H), 4.39 (q, J=7.1 Hz, 2H,), 1.33 (t, J=7.2 Hz, 3H). LC/MS (API-ES, M+H+): 473.0.

후처리

  1. customThe mixture was quenched with aq. NH4Cl
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography with etyl acetate/hexane (1/1, v:v) to ethyl acetate/dichloromethane (9/1)

출처 및 근거

ORD 기록
ord-8f09828f7160448b92247290058866ff
출처 데이터셋
uspto-grants-2008_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07468375B2

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