Triethylamine → HCID 10156526, compound

HRID 433132Notes

Reaction equation

HRID 433132 reaction equation
CC1C=CC(S(O[CH2:12][CH:13]2[CH2:22][CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[O:14]2)(=O)=O)=CC=1.[F:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH2:33][CH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)=[CH:27]2.C(N(CC)CC)C.O.O.C(O)(=O)C(O)=O>CS(C)=O.ClCCl.C(O)C>[O:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:21][CH2:22][CH:13]1[CH2:12][N:37]1[CH2:38][CH2:39][CH:34]([CH2:33][C:28]2[NH:29][C:30]3[C:26]([CH:27]=2)=[CH:25][C:24]([F:23])=[CH:32][CH:31]=3)[CH2:35][CH2:36]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 61373Oxalic acid dihydrateHCID 98345611H-Indole, 5-fluoro-2-(4-piperidinylmethyl)-HCID 9858183HCID 9858183, compound

Product 1

HCID 10156526HCID 10156526, compoundYield 44.6%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3,4-dihydro-2H-chromen-2-ylmethyl 4-methylbenzenesulfonate (0.70 g, 2.19 mmol) in methyl sulfoxide (20 mL) was added 5-fluoro-2-(4-piperidinylmethyl)-1H-indole (0.51 g, 2.19 mmol) and triethylamine (0.25 g, 2.30 mmol) and the reaction mixture was heated to 90° C. for 8 h. The reaction mixture was allowed to cool to room temperature and was diluted with dichloromethane (200 mL), washed with water (2×100 mL), aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, methanol:dichloromethane 1:19) provided a colorless oil which was dissolved in ethyl alcohol (5 mL) and treated with a solution of oxalic acid dihydrate (0.244 g, 1.94 mmol) in ethyl alcohol (10 mL). The resulting solid was filtered, washed (hexanes), and dried to give 0.370 g (44%) of 2-{[1-(3,4-dihydro-2H-chromen-2-ylmethyl)-4-piperidinyl]methyl}-5-fluoro-1H-indole as a white solid. mp 187-190° C.; Anal. Calcd. for C24H27FN2O.0.5 C2O4H2.0.5H2O: C, 69.43; H, 6.76; N, 6.48. Found: C, 69.23; H, 6.83; N, 6.48.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with water (2×100 mL), aqueous sodium chloride (100 mL)
  3. dry with materialdried (magnesium sulfate)
  4. customthe solvent was removed in vacuo
  5. customto give a crude solid
  6. customPurification by flash column chromatography (silica, methanol:dichloromethane 1:19)
  7. customprovided a colorless oil which
  8. filtrationThe resulting solid was filtered
  9. washwashed (hexanes)
  10. customdried

Sources & evidence

ORD record
ord-9516a055fb334d2d809ac922b28223a9
Source dataset
uspto-grants-2003_12
Patent number
US06667322B2

Reaction notes

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