Triethylamine → HCID 69521973, compound

HRID 1793665Notes

Reaction equation

HRID 1793665 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:19][CH:18]([CH2:20][NH:21][C:22]4[CH:26]=[CH:25][O:24][N:23]=4)[O:17][N:16]=3)=[CH:11][CH:10]=2)=[CH:5][CH2:4]1.C(N(CC)CC)C.CC1(C)[O:39][C@H:38]([C:40](Cl)=[O:41])[CH2:37][O:36]1>C(#N)C>[OH:39][C@@H:38]([CH2:40][OH:41])[C:37]([N:3]1[CH2:8][CH2:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:19][CH:18]([CH2:20][NH:21][C:22]4[CH:26]=[CH:25][O:24][N:23]=4)[O:17][N:16]=3)=[CH:11][CH:10]=2)=[CH:5][CH2:4]1)=[O:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10374773HCID 10374773, compoundHCID 22022985HCID 22022985, compound

Product 1

HCID 69521973HCID 69521973, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(5RS)-3-(4-(1,2,5,6-Tetrahydropyrid-4-yl)phenyl)-5-(3-isoxazolylaminomethyl)-4,5-dihydro-isoxazole dihydrochloride (397 mg, 1 mM) was suspended by stirring in acetonitrile (15 ml) under nitrogen, triethylamine (404 mg, 4 mM) added, and the mixture cooled to 0° C. (4S)-2,2-Dimethyl-1,3-dioxolan-4-ylcarbonyl chloride (328 mg, 2 mM) was added dropwise, stirring continued for 30 minutes at 0° C., then for 18 hours allowing the temperature to rise to ambient. Solvent was evaporated, the residue treated with water (25 ml) and extracted into dichloromethane (4×20 ml). The extracts were washed with brine (25 ml), dried (magnesium sulfate), and evaporated. The residue was dissolved in tetrahydrofuran (40 ml), treated with hydrochloric acid (2N, 2 ml), and stirred 48 hours at ambient temperature. Potassium carbonate (2 g) was added, the mixture stirred 30 minutes and filtered. After removal of solvent, the residue was chromatographed on a 10 g silica Mega Bond Elut® column, eluting with a gradient from 5 to 10% methanol in dichloromethane. Relevant fractions were combined to give the desired product (125 mg). MS (ESP): 413 (MH+) for C21H24N4O5 NMR (CDCl3) δ: 2.54 (br, 2H); 3.18 (dd, 1H); 3.26 (m overlapped by H2O, 2H); 3.47 (dd, 2H); 3.55 (m, 1H); 3.74 (m, 2H); 4.13 (br, 1H); 4.26 (m, 1H); 4.38 (m, 1H); 4.67 (d, 1H); 4.89 (overlapping m, 2H); 5.96 (d, 1H); 6.26 (br, 1H); 6.37 (t, 1H); 7.50 (d, 2H); 7.62 (d, 2H); 8.34 (d, 1H).

Workup

  1. additionwas added dropwise
  2. waitfor 18 hours allowing
  3. customSolvent was evaporated
  4. additionthe residue treated with water (25 ml)
  5. extractionextracted into dichloromethane (4×20 ml)
  6. washThe extracts were washed with brine (25 ml)
  7. dry with materialdried (magnesium sulfate)
  8. customevaporated
  9. dissolutionThe residue was dissolved in tetrahydrofuran (40 ml)
  10. additiontreated with hydrochloric acid (2N, 2 ml)
  11. stirringstirred 48 hours at ambient temperature
  12. additionPotassium carbonate (2 g) was added
  13. stirringthe mixture stirred 30 minutes
  14. filtrationfiltered
  15. customAfter removal of solvent
  16. customthe residue was chromatographed on a 10 g silica Mega Bond Elut® column
  17. washeluting with a gradient from 5 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-ffc1d2da8b9142a8bc7dde58751616f9
Source dataset
uspto-grants-2006_07
Patent number
US07081538B1

Reaction notes

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