Trifluoroacetic acid → HCID 68827835, compound

HRID 2100318Notes

Reaction equation

HRID 2100318 reaction equation
[N:1]1([C:7]2([CH2:17][NH:18]C(=O)OC(C)(C)C)[CH2:10][N:9]([S:11]([CH2:14][CH2:15][CH3:16])(=[O:13])=[O:12])[CH2:8]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[N:1]1([C:7]2([CH2:17][NH2:18])[CH2:10][N:9]([S:11]([CH2:14][CH2:15][CH3:16])(=[O:13])=[O:12])[CH2:8]2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57798321HCID 57798321, compound

Product 1

HCID 68827835HCID 68827835, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl {[3-morpholin-4-yl-1-(propylsulfonyl)azetidin-3-yl]methyl}carbamate (0.98 g, 2.6 mmol) was dissolved in dichloromethane (10 ml) and trifluoroacetic acid (2 eq) was added. The reaction was stirred at room temperature overnight. The mixture was evaporated to dryness and the residue treated with saturated aqueous sodium carbonate. The product was extracted into dichloromethane. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and evaporated to give {[3-morpholin-4-yl-1-(propylsulfonyl)azetidin-3-yl]methyl}amine which was used without further purification. 2,4-dichlorobenzoyl chloride (0.14 ml, 1.0 mmol) was added to {[3-morpholin-4-yl-1-(propylsulfonyl)azetidin-3-yl]methyl}amine in dichloromethane (2 ml) and triethylamine (0.22 ml, 1.6 mmol) at 0° C. The reaction was stirred at 0° C. for 15 mins, before warming to room temperature. After 30 mins, lc-ms showed complete consumption of starting material. The reaction was quenched and the resulting mixture was partitioned between dichloromethane and water. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and evaporated to dryness. Purification by preparative tlc led to 2,4-dichloro-N-{[3-morpholin-4-yl-1-(propylsulfonyl)azetidin-3-yl]methyl}benzamide as an oil (15 mg, 4%). This was dissolved in hot ethanol (1 ml) and oxalic acid (2 eq) in ethanol (minimum amount) was added. The ethanol was evaporated and the residue triturated with ether to give the oxalate salt of 2,4-dichloro-N-{[3-morpholin-4-yl-1-(propylsulfonyl)azetidin-3-yl]methyl}benzamide as a white solid (15 mg, 4%). Analytical LCMS: single peak (214 nm), 4.35 min. 1H NMR (400 MHz, DMSO): δ 8.70 (t, J=6.3 Hz, 1 H); 7.71 (d, J=2.0 Hz, 1 H); 7.54-7.46 (m, 2 H); 3.81-3.69 (m, 4 H); 3.59 (d, J=6.3 Hz, 6 H); 3.10-3.04 (m, 2 H); 2.56 (t, J=7.4 Hz, 4 H); 1.74-1.66 (m, 2 H); 0.97 (dd, J=7.4, 7.4 Hz, 3 H).

Workup

  1. customThe mixture was evaporated to dryness
  2. additionthe residue treated with saturated aqueous sodium carbonate
  3. extractionThe product was extracted into dichloromethane
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-776bf21e43a442f6b1a0de6bc1685cb1
Source dataset
uspto-grants-2009_08
Patent number
US07572792B2

Reaction notes

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