Ethyl Acetate → HCID 57692600, 화합물

HRID 2377617노트

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HRID 2377617 반응식
C[C@@:2]1([C:27]([O-:29])=[O:28])[CH2:6][C@@H:5]([O:7][C:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3Br)[CH2:11]2)=[O:9])[CH2:4][N:3]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].[CH3:30][C:31]([CH3:46])([CH3:45])[C@@H:32]([C:42]([OH:44])=[O:43])[NH:33][C:34]([O:36][CH2:37][CH2:38][CH2:39][C:40]#[CH:41])=[O:35].[C:47]([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1.N1CCCC1.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:23]([O:22][C:20]([N:3]1[C@H:2]([C:27]([O:29][CH3:47])=[O:28])[CH2:6][C@@H:5]([O:7][C:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[C:41]#[C:40][CH2:39][CH2:38][CH2:37][O:36][C:34]([NH:33][C@H:32]([C:42]([OH:44])=[O:43])[C:31]([CH3:46])([CH3:45])[CH3:30])=[O:35])[CH2:11]2)=[O:9])[CH2:4]1)=[O:21])([CH3:25])([CH3:24])[CH3:26]

참가 물질

9

반응물 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 574311933-Methyl-N-{[(pent-4-yn-1-yl)oxy]carbonyl}-L-valineHCID 86610193HCID 86610193, 화합물

생성물 1

HCID 57692600HCID 57692600, 화합물수율 99%

시약·촉매·용매 4

HCID 83717Copper iodide촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매HCID 31268Pyrrolidine용매

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온도
70 °C

실험 절차

A solution of 1-tert-butyl 2-methyl-(2S,4R)-4-{[(4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate (100 mg, 0.21 mmol) and 3-methyl-N-[(pent-4-yn-1-yloxy)carbonyl]-L-valine (103 mg, 0.43 mmol) in THF (1 mL) and pyrrolidine (1 mL) was purged with nitrogen. Copper iodide (4 mg, 0.02 mmol) and Pd(PPh3)4 (25 mg, 0.02 mmol) were added and the reaction mixture was heated for 30 min at 70° C. under nitrogen. The resulting mixture was poured into saturated aqueous NaHCO3 and EtOAc, the organic layer separated and washed twice with 10% citric acid solution, then brine and dried over Na2SO4. The residue was purified by column chromatography on silica gel (eluting with 90:10:1 DCM:MeOH:NH4OH) and concentrated to give N-[({5-[2-({[(3R,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidin-3-yl]oxy}carbonyl)-2,3-dihydro-1H-isoindol-4-yl]pent-4-yn-1-yl}oxy)carbonyl]-3-methyl-L-valine (131 mg, 99% yield) as colorless oil. LRMS (ESI) m/z 530.5 [(M+H)+; calcd for C27H36N3O8: 530.6].

후처리

  1. customthe organic layer separated
  2. washwashed twice with 10% citric acid solution
  3. dry with materialbrine and dried over Na2SO4
  4. customThe residue was purified by column chromatography on silica gel (eluting with 90:10:1 DCM:MeOH:NH4OH)
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-f634b735e9e94f97a90738a2b6425283
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07470664B2

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