Formaldehyde → HCID 10179729, compound

HRID 1832207Notes

Reaction equation

HRID 1832207 reaction equation
[CH3:1][CH:2]([CH3:18])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:7]=1)=[O:4].[CH2:19]=O.[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([CH:26]=[CH:27][NH:28]2)=[CH:24][CH:23]=1>CC(O)=O.O1CCOCC1.O>[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([CH2:19][N:15]3[CH2:16][CH2:17][CH:12]([C:8]4[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:18])[CH3:1])[CH:11]=[CH:10][CH:9]=4)[CH2:13][CH2:14]3)=[CH:27][NH:28]2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 871116-ChloroindoleHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamide

Product 1

HCID 10179729HCID 10179729, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22565020HOAc dioxaneSolvent

Procedure

A solution of 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (0.369 g, 1.50 mmol) and 37 wt % aqueous formaldehyde (30.0 mg, 1.50 mmol) in 1 mL of HOAc:dioxane (1:4) was added to 6-chloro-1-H-indole (0.152 g, 1.00 mmol) and the reaction mixture was stirred for 12 h at room temperature. The resulting mixture was diluted with H2O (10 mL). The aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by preparative TLC on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product (79 mg, 42%). 1H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 8.04 (s, 1H), 7.52 (t, 2H, J=8.1 Hz), 7.35 (d, 2H, J=13.3 Hz), 7.18 (t, 1H, J=7.9 Hz), 7.09 (dd, 1H, J=1.9, 8.5 Hz), 6.85 (d, 1H, J=7.4 Hz), 5.18 (s, 1H), 4.01 (s, 2H), 2.55 (septet, 1H, J=6.8 Hz), 2.48–2.34 (m, 3H), 2.08–1.95 (m, 4H), 1.78 (d, 2H, J=12.8 Hz), 1.22 (d, 6H, J=6.8 Hz); ESMS m/e: 410.1 (M+H)+.

Workup

  1. extractionThe aqueous layer was extracted with CH2Cl2 (3×100 mL)
  2. washThe combined organic extracts were washed with brine (10 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative TLC on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2

Sources & evidence

ORD record
ord-4fe24d5fb99640fbb572f71fcfede806
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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