Formaldehyde → HCID 22048782, compound

HRID 1832652Notes

Reaction equation

HRID 1832652 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.[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[CH:29]=[CH:30][CH:31]=[C:32]2[C:36]=1[NH:35][CH:34]=[CH:33]2>CC(O)=O.O1CCOCC1.O>[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[CH:29]=[CH:30][CH:31]=[C:32]2[C:36]=1[NH:35][CH:34]=[C:33]2[CH2:19][N:15]1[CH2:16][CH2:17][CH:12]([C:8]2[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:18])[CH3:1])[CH:11]=[CH:10][CH:9]=2)[CH2:13][CH2:14]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamideHCID 22048903HCID 22048903, compound

Product 1

HCID 22048782HCID 22048782, compoundYield 126%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22565020HOAc dioxaneSolvent

Procedure

Prepared by Procedure D and Scheme N. A solution of 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (23.3 mg, 0.0948 mmol) and 37 wt % aqueous formaldehyde (11.4 mg, 0.142 mmol) in 1.00 mL of HOAc:dioxane (1:4) was added to 7-(2-fluorophenyl)-1H-indole (20.0 mg, 0.0948 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 (3×10 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 4% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product (56.1 mg, 100%): 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 7.73 (dd, 1H, J=2.8, 6.3 Hz), 7.69 (s, 1H), 7.53 (dt, 1H, J=1.8, 7.6 Hz), 7.44 (d, 1H, J=8.1 Hz), 7.38 (m, 2H), 7.32 (s, 1H), 7.27–7.21 (m, 4H), 7.17 (t, 1H, J=7.6 Hz), 6.88 (d, 1H, J=7.6 Hz), 3.92 (s, 2H); 3.20 (d, 1H, J=11.6 Hz), 2.51 (qt, 1H, J=6.7 Hz), 2.42 (m, 1H), 2.25 (dt, 2H, J=2.2, 11.6 Hz), 1.89–1.72 (m, 5H), 1.22 (d, 6H, J=7.3 Hz); ESMS m/e: 470.1 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-4621faf1177345acbae1642207ee083a
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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