Cesium carbonate → 5-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-[(E)-4-methoxycinnamoyl]-1,2-dihydro-3H-benz[e]indole

HRID 366831Notes

Reaction equation

HRID 366831 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]2[CH:29]=[CH:28][CH:27]=[CH:26][C:11]=2[C:12]2[CH:13]([CH2:24][Cl:25])[CH2:14][N:15]([C:18](=[O:23])[C:19](F)(F)F)[C:16]=2[CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:36][O:37][C:38]1[CH:48]=[CH:47][C:41](/[CH:42]=C/C(Cl)=O)=[CH:40][CH:39]=1>CN1CCCC1=O.O.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]2[CH:29]=[CH:28][CH:27]=[CH:26][C:11]=2[C:12]2[CH:13]([CH2:24][Cl:25])[CH2:14][N:15]([C:18](=[O:23])/[CH:19]=[CH:42]/[C:41]3[CH:47]=[CH:48][C:38]([O:37][CH3:36])=[CH:39][CH:40]=3)[C:16]=2[CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 105505045-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-trifluoroacetyl-1,2-dihydro-3H-benz[e]indoleHCID 10976422trans-4-Methoxycinnamoyl chloride

Product 1

HCID 117993395-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-[(E)-4-methoxycinnamoyl]-1,2-dihydro-3H-benz[e]indoleYield 48.5%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
20 °C

Procedure

A stirred solution of the above 5-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-trifluoroacetyl-1,2-dihydro-3H-benz[e]indole (100 mg, 0.23 mmol) in N-methylpyrrolidone (2.5 mL) was treated dropwise at 20° C. with a solution of Cs2CO3 (650 mg) in water (1.5 mL). the mixture was stirred for a further 45 min at 20° C. then diluted with water (20 mL) and extracted with benzene (2×15 mL). The combined organic extracts were washed with water (2×), dried (Na2SO4) and concentrated under reduced pressure below 30° C. The residue was dissolved in pyridine (2 mL), cooled to -5° C. and treated with (E)-4-methoxycinnamoyl chloride (46 mg, 0.23 mmol) followed by DMAP (15 mg). The mixture was stirred for a further 30 min at 20° C., then diluted with KHCO3 solution. The precipitated solid was collected, washed with water, dried and chromatographed on silica gel. Elution with CH2Cl2 /EtOAc gave the crude product which was recrystallised from CH2Cl2 /petroleum either to give 5-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-[(E)-4-methoxycinnamoyl]-1,2-dihydro-3H-benz[e]indole (55 mg, 48%), mp 185-185.5° C. 1H NMR [(CD3)2SO] δ 9.28 (br s, 1 H, NH), 8.64 (br s, 1 H, H-4), 8.01 (d, J=8.1 Hz, 1 H, H-6), 7.92 (d, J=8.3 Hz, 1 H, H-9), 7.78 (d, J=8.6 Hz, 2 H, H-2',6'), 7.66 (d, J=15.3 Hz, 1 H, PhCH=CH), 7.54 (t, J=7.6 Hz, 1 H, H-8), 7.42 (t, J=7.7 Hz, 1 H, H-7), 7.10 (d, J=15.2 Hz, 1 H, PhCH=CH), 7.01 (d, J=8.7 Hz, 2 H, H-3',5'), 4.60-4.44 (m, 2 H, H-2), 4.41-4.28 (m, 1 H, H-1), 4.02 (dd, J=11.1, 3.0 Hz, 1 H, CHHCl), 3.92 (dd, J=11.1, 7.2 Hz, 1 H, CHHCl), 3.82 (s, 3 H, OCH3), 1.51 (s, 9 H, C(CH3)3).

Workup

  1. extractionextracted with benzene (2×15 mL)
  2. washThe combined organic extracts were washed with water (2×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure below 30° C
  5. dissolutionThe residue was dissolved in pyridine (2 mL)
  6. temperaturecooled to -5° C.
  7. stirringThe mixture was stirred for a further 30 min at 20° C.
  8. customThe precipitated solid was collected
  9. washwashed with water
  10. customdried
  11. customchromatographed on silica gel
  12. washElution with CH2Cl2 /EtOAc
  13. customgave the crude product which
  14. customwas recrystallised from CH2Cl2 /petroleum

Sources & evidence

ORD record
ord-c8bd66f5dcc048fb91aee9000d67a832
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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