Water → HCID 59860370, compound

HRID 252121Notes

Reaction equation

HRID 252121 reaction equation
[Cl:1][C:2]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][Si](C)(C)C)=[CH:13][N:12]=2)[CH2:7]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[Cl:1][C:2]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[CH:18])=[CH:13][N:12]=2)[CH2:7]1

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 66854789HCID 66854789, compound

Product 1

HCID 59860370HCID 59860370, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dissolve (S)-(2,4-dichlorbenzyl)-[1-(5-trimethylsilanylethynyl-pyridin-2-yl)-pyrrolidin-3-yl]-amine (190 mg, 0.45 mmol) in THF (10 mL). Add tetrabutylammonium fluoride (1 mL, 1.0 M in THF) dropwise. Stir for 2 h at room temperature. Add water. Extract with ethyl acetate (3×), wash the organic layers with saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and chromatograph on silica gel, eluting with a 20:80 to 1:1 ethyl acetate:hexanes, to give the title compound as a yellow oil (141 mg, 90%). Dissolve the oil in methanol and add fumaric acid (47 mg, 0.41 mmol) in methanol. Concentrate most of the solvent, add acetonitrile and stir overnight. Filter the solid and dry in a vacuum oven at 60° C. overnight to give the title compound as its fumarate salt (139 mg, 74%). 1H NMR (400 MHz, MeOH-d4) 8.15 (d, 1H, J=2.4 Hz), 7.59-7.54 (m, 3H), 7.39 (dd, 1H, J=8.0, 2.0 Hz), 6.72 (s, 2H), 6.50 (d, 1H, J=8.8 Hz), 4.20-4.12 (m, 2H), 3.83-3.76 (m, 2H), 3.70-3.64 (m, 1H), 3.59-3.47 (m, 2H), 3.44 (s, 1H), 2.46-2.38 (m, 1H), 2.18-2.09 (m, 1H), MS (ES): m/z=346 [M+H].

Workup

  1. extractionExtract with ethyl acetate (3×)
  2. washwash the organic layers with saturated aqueous sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. concentrationconcentrate
  5. washchromatograph on silica gel, eluting with a 20:80 to 1:1 ethyl acetate

Sources & evidence

ORD record
ord-a54e478ca4b8426e971e55975e66b103
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

Loading…