Acetic Acid → 5-Amino-1-(chloromethyl)-3-[(e)-3-methoxycinnamoyl]-1,2-dihydro-3h-benz[e]indole

HRID 366829Notes

Reaction equation

HRID 366829 reaction equation
[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]([N+:16]([O-])=O)=[CH:7][C:6]=2[N:5]([C:19](=[O:30])/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=2)[CH2:4]1.CO.O.CC(O)=O>C1COCC1.[Fe]>[NH2:16][C:8]1[C:9]2[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=2[C:11]2[CH:3]([CH2:2][Cl:1])[CH2:4][N:5]([C:19](=[O:30])/[CH:20]=[CH:21]/[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[C:6]=2[CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 962WaterHCID 100252921-(chloromethyl)-3-[(E)-3-methoxycinnamoyl]-5-nitro-1,2-dihydro-3H-benz[e]indole

Product 1

HCID 54701445-Amino-1-(chloromethyl)-3-[(e)-3-methoxycinnamoyl]-1,2-dihydro-3h-benz[e]indoleYield 54%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a hot solution of 14l (110 mg, 0.26 mmol) in THF (10 mL) was added in sequential fashion MeOH (5 mL), H2O (2 mL), AcOH (0.2 mL) and Fe powder (0.5 mL). The mixture was heated at reflux for 1 h, then basified with CaO (1 g), filtered, concentrated to a small volume under reduced pressure below 30° C. and diluted with water. The resulting precipitate was chromatographed on silica gel, eluting with CH2Cl2 /EtOAc (9:1), to give a solid which was recrystallised from CH2Cl2 /petroleum ether to give 15l (55 mg, 54%) mp >200° C. 1H NMR [(CD3)2SO] δ 8.06 (d, J=8.5 Hz, 1 H, H-6), 7.83 (bs, 1 H, H-4), 7.72 (d, J=8.3 Hz, 1 H, H-9), 7.63 (d, J=15.4 Hz, 1 H, PhC=CH), 7.44 (t, J=7.4 Hz, 1 H, H-8), 7.40-7.34 (m, 3 H, PhH), 7.26 (t, partially obscured, J=7.9 Hz, 1 , H-7), 7.22 (d, J=15.4 Hz, 1 h, PhCH=CH), 7.04-6.97 (m, 1 H, PhH), 5.95 (br s, 2 H, NH2), 4.53-4.38 (m, 2 H, H-2), 4.19-4.08 (m, 1 H, H-1), 3.95 (dd, J=11.0, 2.9 Hz, 1 H, CHHCl), 3.83 (s, 3 H, OCH3), 3.76 (dd, J=10.9, 8.1 Hz, 1 H, CHHCl). Anal. Calculated for C23H21ClN2O2 : C, 70.3; H, 5.4; N, 7.1; Cl, 9.0. Found: C, 70.4; H, 5.6; N, 6.9; Cl, 9.1%.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. filtrationfiltered
  4. concentrationconcentrated to a small volume under reduced pressure below 30° C.
  5. additiondiluted with water
  6. customThe resulting precipitate was chromatographed on silica gel
  7. washeluting with CH2Cl2 /EtOAc (9:1)
  8. customto give a solid which
  9. customwas recrystallised from CH2Cl2 /petroleum ether

Sources & evidence

ORD record
ord-da936fa627964949bf2d0ab10b93d3c3
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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