Ammonia → HCID 21071651, compound

HRID 1666860Notes

Reaction equation

HRID 1666860 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:11](=[CH:12][CH:13]=1)[C:7]([CH2:8][CH2:9][NH2:10])=[CH:6][NH:5]2.[F:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O.[BH4-].[Na+].N.[Cl-].[NH4+]>C(O)C.CO.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:11]([C:7]([CH2:8][CH2:9][NH:10][CH2:22][C:21]3[CH:24]=[CH:25][CH:26]=[C:19]([O:18][CH2:17][CH2:16][CH2:15][F:14])[CH:20]=3)=[CH:6][NH:5]2)=[CH:12][CH:13]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 1457051H-Indole-3-ethanamine, 6-chloro-HCID 4311764Sodium borohydrideHCID 21071511HCID 21071511, compound

Product 1

HCID 21071651HCID 21071651, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Combine 6-chlorotryptamine (1.4 g, 7.2 mmol), 3-(3-fluoropropoxy)benzaldehyde (1.3 g, 7.2 mmol), and molecular sieves in ethanol (150 mL), and heat at 78° C. overnight. Filter the reaction mixture through a plug of celite, and treat the resulting filtrate with sodium borohydride (817 mg, 21.6 mmol) and stir overnight at room temperature. Evaporate the solvent in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 9:1 mixture of dichloromethane and 1N ammonia in methanol to give a residue. Chromatograph that residue on 10 g SCX column (wash column with methanol then elute with 1 N ammonia in methanol) and concentrate in vacuo to give a light yellow oil. Dissolve the oil in methanol and treated with a methanolic solution of ammonium chloride (112 mg, 2.1 mmol). Sonicate the resulting mixture for 10 minutes, remove the solvent in vacuo, and triturate the resulting residue with ether containing a few drops of acetonitrile to give a solid. Collect the solid by filtration to give the title compound as the hydrochloride: mp 177.8-178.9° C.; 1H NMR (400 MHz, dmso-d6): 11.15 (br s, 1H), 9.41 (br s, 2H), 7.57 (d, 1H, J=8.0 Hz), 7.39 (d, 1H, J=2.0 Hz), 7.32 (t, 1H, J=7.8 Hz), 7.26 (d, 1H, J=2.4 Hz), 7.25-7.21 (m, 1H), 7.11 (d, 1H, J=8.0 Hz), 7.01 (dd, 1H, J=8.8, 2.0 Hz), 6.97 (dd, 1H, J=8.0, 2.0 Hz), 4.60 (dt, 2H, J=47.6, 6.0 Hz), 4.13 (br s, 2H), 4.08 (t, 2H, J=6.4 Hz), 3.10 (br s, 4H), 2.11 (d quintuplets, 2H, J=26.0, 6.0 Hz); MS (ES+): m/e 361.3 (M+1); CHN (for C20H22ClFN2O.HCl) calcd: C, 60.46; H, 5.83; N, 7.05. found: C, 60.48; H, 5.86; N, 7.16.

Workup

  1. filtrationFilter the reaction mixture through a plug of celite
  2. customEvaporate the solvent in vacuo
  3. customto give a residue
  4. customto give a residue
  5. washChromatograph that residue on 10 g SCX column (wash column with methanol
  6. washthen elute with 1 N ammonia in methanol) and
  7. concentrationconcentrate in vacuo
  8. customto give a light yellow oil
  9. customSonicate the resulting mixture for 10 minutes
  10. customremove the solvent in vacuo
  11. customtriturate the resulting residue with ether containing a few drops of acetonitrile
  12. customto give a solid
  13. customCollect the solid
  14. filtrationby filtration

Sources & evidence

ORD record
ord-f24a2fcc492d4f8ab375d75a00de9973
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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