Mechlorethamine → 3-(4-Fluorophenyl)-5-methyl-1-(1-methylpiperazin-4-yl)-1H-indole

HRID 275364Notes

Reaction equation

HRID 275364 reaction equation
[NH2:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([CH3:11])=[CH:8][CH:9]=2)[C:4]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:3]1.[NH2-].[Na+].Cl[CH2:22][CH2:23][N:24]([CH3:28])[CH2:25][CH2:26]Cl>C1(C)C(C)=CC=CC=1.C1(C)C=CC=CC=1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[C:7]([CH3:11])[CH:6]=3)[N:2]([N:1]3[CH2:26][CH2:25][N:24]([CH3:28])[CH2:23][CH2:22]3)[CH:3]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 4033MechlorethamineHCID 24533Sodium amideHCID 100830041-Amino-3-(4-fluorophenyl)-5-methyl-1H-indole

Product 1

HCID 102456373-(4-Fluorophenyl)-5-methyl-1-(1-methylpiperazin-4-yl)-1H-indole

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 7237O-XyleneSolvent

Procedure

To a mixture of 1-amino-3-(4-fluorophenyl)-5-methyl-1H-indole 19a (1 g) and toluene (20 ml) was added a 50% suspension of sodium amide in xylene (1.0 ml). After reaction for 15 min at room temperature a solution of N,N-bis(2-chloroethyl)methylamine (0.8 g) in toluene was added slowly and the mixture was refluxed for 3 h. After cooling to room temperature, the solvents were evaporated in vacuo and water (100 ml) was added. The mixture was extracted with ethyl acetate (2×50 ml) and the combined organic phases were dried (Na2SO4). Evaporation of the solvents in vacuo afforded the title compound, which was purified by column chromatography on silica gel (eluted with ethyl acetate/ethanol 4:1 containing 4% triethylamine) and crystallized from heptane. Yield: 0.5 g, mp 105°-107° C.

Workup

  1. additionwas added slowly
  2. temperaturethe mixture was refluxed for 3 h
  3. customthe solvents were evaporated in vacuo and water (100 ml)
  4. additionwas added
  5. extractionThe mixture was extracted with ethyl acetate (2×50 ml)
  6. dry with materialthe combined organic phases were dried (Na2SO4)
  7. customEvaporation of the solvents in vacuo

Sources & evidence

ORD record
ord-033f78d445534a13a9f2f1d514996018
Source dataset
uspto-grants-1995_02
Patent number
US05393761

Reaction notes

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