Oxalic Acid → HCID 11554195, compound

HRID 2100319Notes

Reaction equation

HRID 2100319 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[N:12]1([C:18]2([CH2:28][NH2:29])[CH2:21][N:20]([S:22]([CH2:25][CH2:26][CH3:27])(=[O:24])=[O:23])[CH2:19]2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C(N(CC)CC)C.C(O)(=O)C(O)=O>ClCCl.C(O)C>[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:29][CH2:28][C:18]1([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH2:21][N:20]([S:22]([CH2:25][CH2:26][CH3:27])(=[O:24])=[O:23])[CH2:19]1)=[O:5]

Participants

7

Reactant 4

HCID 971Oxalic AcidHCID 8471TriethylamineHCID 666452,4-Dichlorobenzoyl chlorideHCID 68827835HCID 68827835, compound

Product 1

HCID 11554195HCID 11554195, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

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. customwas used without further purification
  2. temperaturebefore warming to room temperature
  3. waitAfter 30 mins
  4. customconsumption of starting material
  5. customThe reaction was quenched
  6. customthe resulting mixture was partitioned between dichloromethane and water
  7. washThe organic phase was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customevaporated to dryness
  10. customPurification by preparative tlc
  11. dissolutionThis was dissolved in hot ethanol (1 ml)
  12. customThe ethanol was evaporated
  13. customthe residue triturated with ether

Sources & evidence

ORD record
ord-1ef83f04fc844bbf959f6c6d3b334ff7
Source dataset
uspto-grants-2009_08
Patent number
US07572792B2

Reaction notes

Loading…