Dimethylformamide → 3-[3-(4-Methylpiperazin-1-yl)-propyl]-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde

HRID 1372412Notes

Reaction equation

HRID 1372412 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][N:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][C:16]2[C:24]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=3[NH:18][CH:17]=2)[CH2:9][CH2:8]1.CN(C)[CH:27]=[O:28]>>[CH3:6][N:7]1[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH2:15][C:16]2[C:24]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=3[NH:18][C:17]=2[CH:27]=[O:28])[CH2:11][CH2:12]1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 225711153-[3-(4-methylpiperazin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indole

Product 1

HCID 225711323-[3-(4-Methylpiperazin-1-yl)-propyl]-4,5,6,7-tetrahydro-1H-indole-2-carbaldehydeYield 62%

Procedure

Phosphorus oxychloride (1.8 mL, 18.9 mmol) was added dropwise to cooled dimethylformamide (3.8 mL, 51.6 mmol). After stirring at room temperature for 30 minutes, it was cooled to −5° C. and a solution of 3-[3-(4-methyl-piperazin-1-yl)-propyl]-4,5,6,7-tetrahydro-1H-indole (4.5 g, 17.2 mmol) in dimethylformamide (9 mL) was added dropwise. The mixture was stirred at room temperature overnight. The reaction was quenched with ice, followed by 10 N sodium hydroxide to pH 10–11. After stirring at room temperature for 1 hour, the reaction was extracted with ethyl acetate, washed with brine, dried and concentrated to give 3.1 g (62% yield) of 3-[3-(4-methyl-piperazin-1-yl)-propyl]-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde. 1H-NMR (360 MHz, diemthylsulfoxide-d6) δ 11.24 (br, s, 1H, NH), 9.42 (s, 1H, CHO), 2.60 (t, 2H, CH2), 2.51 (m, 2H, CH2), 2.35 (m, 2H, CH2), 2.28 (m, 8H, 4×CH2), 2.21 (m, 2H, CH2), 2.12 (s, 3H, CH3), 1.57–1.68 (m, 6H, 3×CH2). MS m/z 289 [M+].

Workup

  1. temperatureit was cooled to −5° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. customThe reaction was quenched with ice
  4. stirringAfter stirring at room temperature for 1 hour
  5. extractionthe reaction was extracted with ethyl acetate
  6. washwashed with brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a6e02791950145aa8593a2d78ee2ec27
Source dataset
uspto-grants-2007_01
Patent number
US07157577B2

Reaction notes

Loading…