Sodium Carbonate → 2-[4-(2-Diethylamino-ethyl)-phenyl]-3,4,5,6-tetrahydro-azepino[5,4,3-cd]indol-6-one

HRID 33313

반응식

HRID 33313 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH2:13][CH3:14])[CH2:11][CH3:12])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:39]1[NH:40][C:41]2[CH:42]=[CH:43][CH:44]=[C:45]3[C:51](=[O:52])[NH:50][CH2:49][CH2:48][C:47]=1[C:46]=23.C(=O)([O-])[O-].[Na+].[Na+]>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].CO.C(Cl)(Cl)Cl.O>[CH2:11]([N:10]([CH2:13][CH3:14])[CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:39]2[NH:40][C:41]3[CH:42]=[CH:43][CH:44]=[C:45]4[C:51](=[O:52])[NH:50][CH2:49][CH2:48][C:47]=2[C:46]=34)=[CH:3][CH:4]=1)[CH3:12]

참가 물질

9

반응물 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 99432302-Bromo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-oneHCID 222667072-(4-Bromophenyl)-N,N-diethylethanamine

생성물 1

HCID 222666792-[4-(2-Diethylamino-ethyl)-phenyl]-3,4,5,6-tetrahydro-azepino[5,4,3-cd]indol-6-one

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 962Water용매HCID 21584188Chloroform methanol용매

반응 조건

온도
80 °C

실험 절차

(As described in Tet. Lett. 1997 p. 3841) [2-(4-Bromo-phenyl)-ethyl]-diethylamine (256 mg, 1.00 mmol), diboron pinacol ester (279 mg, 1.10 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (24 mg, 0.03 mmol), and potassium acetate (294 mg, 3.00 mmol) were combined in a schlenk tube. The vessel was evacuated then refilled with argon thrice. Degassed DMF (6 mL) was added and the mixture stirred at 80° C. under an argon atmosphere for 2 h. 2-Bromo-3,4,5,6-tetrahydro-azepino[5,4,3-cd]indol-6-one (239 mg, 0.90 mmol), a second portion of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (24 mg, 0.03 mmol), and sodium carbonate (2.5 mL of a 2.0 M aqueous solution, 5.00 mmol) were then added and the reaction stirred under an argon atmosphere at 80° C. for another 17 h. The reaction reaction mixture was then poured into 25 mL water then extracted with 25% IPA/CHCl3 (3×20 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacou leaving a brown oil. The crude product was passed through a short silica plug with 25% MeOH/CHCl3 then purified by radial chromatography eluting with 20% MeOH/CHCl3. Crystallization from MeOH/CHCl3/hexanes yielded 2-[4-(2-diethylamino-ethyl)-phenyl]-3,4,5,6-tetrahydro-azepino[5,4,3-cd]indol-6-one, 69 mg (19%) as a white solid: m.p. 224-224.5° C. (dec); 1H NMR (300 MHz, d6-DMSO) δ 0.98 (t, J=6.9 Hz, 6H), 2.53 (q, J=7.2 Hz, 4H), 2.69 (m, 4H), 3.04 (m, 2H), 3.37 (m, 2H), 7.19 (t, J=7.8 Hz, 1H), 7.36 (d, J=8.1 Hz, 2H), 7.55 (m, 3H), 7.88 (dd, J=7.5, 0.9 Hz, 1H), 8.06 (br t, 1H), 11.51 (br s, 1H). MS (FAB, MH+): 362. Anal. (C23H27N3O) C, H, N.

후처리

  1. customThe vessel was evacuated
  2. additionthen refilled with argon thrice
  3. additionDegassed DMF (6 mL) was added
  4. stirringthe reaction stirred under an argon atmosphere at 80° C. for another 17 h
  5. customThe reaction reaction mixture
  6. extractionthen extracted with 25% IPA/CHCl3 (3×20 mL)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. concentrationconcentrated in vacou
  9. customleaving a brown oil
  10. customthen purified by radial chromatography
  11. washeluting with 20% MeOH/CHCl3
  12. customCrystallization from MeOH/CHCl3/hexanes

출처 및 근거

ORD 기록
ord-dccc3678d85b4e008e0015e734dc9ada
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07429578B2

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