Methylamine → (3S)-3-[(1-Benzothien-2-carbonitrile-7-yl)oxy]-N-methyl-3-phenyl-1-propanamine fumarate

HRID 1822985Notes

Reaction equation

HRID 1822985 reaction equation
I[CH2:2][CH2:3][C@H:4]([O:11][C:12]1[C:20]2[S:19][C:18]([C:21]#[N:22])=[CH:17][C:16]=2[CH:15]=[CH:14][CH:13]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:23][NH2:24].[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29]>O1CCCC1.CO>[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29].[S:19]1[C:20]2[C:12]([O:11][C@H:4]([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:3][CH2:2][NH:24][CH3:23])=[CH:13][CH:14]=[CH:15][C:16]=2[CH:17]=[C:18]1[C:21]#[N:22]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 444972Fumaric AcidHCID 586307067-{[(1S)-3-iodo-1-phenylpropyl]oxy}-1-benzothiophene-2-carbonitrile

Product 1

HCID 86594247(3S)-3-[(1-Benzothien-2-carbonitrile-7-yl)oxy]-N-methyl-3-phenyl-1-propanamine fumarateYield 85%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-{[(1S)-3-iodo-1-phenylpropyl]oxy}-1-benzothiophene-2-carbonitrile (222 mg, 0.5 mmol) in tetrahydrofuran (2 mL) was added 40% aqueous methylamine (0.83 mL) and the solution was stirred at room temperature for 16 hours. The solvent removed in vacuo and the residue purified by flash chromatography with a gradient of 0–15% methanol in dichloromethane. To a solution of free base (155 mg, 0.48 mmol) in methanol (1 mL) and added a warm solution of fumaric acid (40 mg, 0.48 mmol) in methanol (1 mL). The solvent removed in vacuo, and the solid residue triturated with diethyl ether (5 mL), then dried in a vacuum oven at 40° C. for 1 h to give the title compound (0.20 g, 85%); δH (300 MHz, DMSO) 8.40 (1H, s, 3-ArH), 7.61–7.52 (1H, m, ArH), 7.49–7.23 (6H, m, ArH), 7.05–6.98 (1H, m, ArH), 6.43 (2H, s, CHCO2H), 5.85–5.75 (1H, m, CHO), 3.05–2.90 (2H, m, 1-CH2), 2.52 (3H, s, NHCH3) and 2.46–2.07 (2H, m, 2-CH2).

Workup

  1. customThe solvent removed in vacuo
  2. customthe residue purified by flash chromatography with a gradient of 0–15% methanol in dichloromethane
  3. customThe solvent removed in vacuo
  4. customthe solid residue triturated with diethyl ether (5 mL)
  5. customdried in a vacuum oven at 40° C. for 1 h

Sources & evidence

ORD record
ord-13bb0ffa870b483ba016f6a74a970b9a
Source dataset
uspto-grants-2006_05
Patent number
US07037932B2

Reaction notes

Loading…