Ethyl Acetate → Jnj-18038683

HRID 600063노트

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HRID 600063 반응식
C([O:5]C([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:13]=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[C:32]([O-:35])([O-:34])=O.[Na+].[Na+].ClC1C=CC(B2[O:49][C:48]3[CH:50]=CC=C[C:47]=3[O:46]2)=CC=1.C(OC(N1CCC2N(CC3C=CC=CC=3)N=C(OS(C(F)(F)F)(=O)=O)C=2CC1)=O)(C)(C)C.CC[O:88][C:89]([CH3:91])=[O:90]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[C:89]([OH:88])(=[O:90])[CH2:91][C:48]([CH2:50][C:32]([OH:35])=[O:34])([C:47]([OH:46])=[O:5])[OH:49].[CH2:18]([N:14]1[C:15]2[CH2:16][CH2:17][NH:8][CH2:9][CH2:10][C:11]=2[C:12]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)=[N:13]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

참가 물질

10

반응물 5

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 32553502-(4-Chlorophenyl)-1,3,2-benzodioxaboroleHCID 672688521-Benzyl-6-Boc-3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepineHCID 865983901-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester

생성물 1

HCID 11249539Jnj-18038683수율 92%

시약·촉매·용매 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. To a 1-L, three-necked, round-bottomed flask was added Pd(dppf)Cl2 (2.8 g, 3.4 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.96 g, 1.73 mmol), Bu4N+Br− (2.78 g, 8.6 mmol), Na2CO3 (36.5 g, 344 mmol) and 2-(4-chloro-phenyl)-benzo[1,3,2]dioxaborole (23.8 g, 103 mmol), under N2. A solution of 1-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (41 g, 86 mmol) in toluene (250 mL) was added, followed by the addition of H2O (250 mL) via syringe. The reaction mixture was stirred at reflux for 3 h and then was cooled to rt. The organic layer was diluted with EtOAc (200 mL) and then was washed with 1 M aq. K2CO3 until the color of the aqueous layer stabilized. The organic layer was washed with brine (200 mL), dried over MgSO4, filtered, and concentrated. The crude product thus obtained was pad-filtered through a short plug of SiO2 to afford the title compound (34.5, 79 mmol, 92%) as a white solid. MS (ESI): exact mass calculated for C25H28ClN3O2, 437.19. found, m/z 438.1, [M+H]+. HPLC (Method B): Rt=10.89 min. 1H NMR (400 MHz, CDCl3): 7.50-7.45 (m, 2H), 7.40-7.36 (m, 2H), 7.36-7.25 (m, 3H), 7.13-7.10 (m, 2H), 5.35-5.33 (m, 2H), 3.56-3.50 (m, 4H), 2.83-2.75 (m, 4H), 1.28-1.25 (m, 9H).

후처리

  1. temperatureat reflux for 3 h
  2. washwas washed with 1 M aq. K2CO3 until the color of the aqueous layer
  3. washThe organic layer was washed with brine (200 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product thus obtained
  8. filtrationwas pad-filtered through a short plug of SiO2

출처 및 근거

ORD 기록
ord-9ff20b238f7642a1b9044e70e25265de
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897771B2

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