Dimethylformamide → HCID 22571094, compound

HRID 1372409Notes

Reaction equation

HRID 1372409 reaction equation
P(Cl)(Cl)(Cl)=O.[N:6]1([CH2:11][CH2:12][CH2:13][C:14]2[C:22]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[NH:16][CH:15]=2)[CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[K+].CN(C)[CH:27]=[O:28]>>[N:6]1([CH2:11][CH2:12][CH2:13][C:14]2[C:22]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[NH:16][C:15]=2[CH:27]=[O:28])[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 14797Potassium HydroxideHCID 24813Phosphorus oxychlorideHCID 22571107HCID 22571107, compound

Product 1

HCID 22571094HCID 22571094, compoundYield 76%

Procedure

Phosphorus oxychloride (2.0 mL, 21.2 mmol) was added dropwise to ice-cooled dimethylformamide (4.5 mL) and stirred at room temperature for 30 minutes. To the mixture at −5° C. was added a suspension of 3-(3-pyrrolidin-1-yl-propyl)-4,5,6,7-tetrahydro-1H-indole (4.5 g, 19.3 mmol) in 10 mL of dimethylformamide. The mixture was stirred at room temperature overnight. Ice cubes were added to the reaction followed by 10 N potassium hydroxide to pH 11–12. The mixture was stirred for 1 hour, extracted with ethyl acetate and the extract washed with brine and concentrated. The residue was dissolved in dichloromethane and filtered through silica gel eluting with 7% methanol in dichloromethane to give 3.8 g (76% yield) of the product. 1H-NMR (300 MHz, diemthylsulfoxide-d6) δ 11.28 (br, s, 1H, NH), 9.38 (s, 1H, CHO), 2.59 (t, 2H, CH2), 2.46 (m, 2H, CH2), 2.3–2.44 (m, 8H, 4×CH2), 1.55–1.65 (m, 10H, 5×CH2). MS m/z 260 [M+].

Workup

  1. additionTo the mixture at −5° C. was added
  2. stirringThe mixture was stirred at room temperature overnight
  3. additionIce cubes were added to the reaction
  4. stirringThe mixture was stirred for 1 hour
  5. extractionextracted with ethyl acetate
  6. washthe extract washed with brine
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in dichloromethane
  9. filtrationfiltered through silica gel eluting with 7% methanol in dichloromethane

Sources & evidence

ORD record
ord-c934581bba904e97913a4a631d5511d5
Source dataset
uspto-grants-2007_01
Patent number
US07157577B2

Reaction notes

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