Methanol → HCID 131715390, compound

HRID 247388Notes

Reaction equation

HRID 247388 reaction equation
[CH2:1]=[C:2]1[CH2:10][CH2:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][CH2:13][C:5]=3[C:4]=2[C:3]1=[O:14].[C:15]1([N:21]2[C:25]3([CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:24](=[O:31])[NH:23][CH2:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(Cl)(Cl)[Cl:33].CO>C(O)C.C(O)(=O)C.O>[ClH:33].[O:31]=[C:24]1[C:25]2([CH2:26][CH2:27][N:28]([CH2:1][CH:2]3[CH2:10][CH2:9][C:8]4[NH:7][C:6]5[CH2:11][CH2:12][CH2:13][C:5]=5[C:4]=4[C:3]3=[O:14])[CH2:29][CH2:30]2)[N:21]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:22][NH:23]1

Participants

8

Reactant 4

HCID 887MethanolHCID 6212ChloroformHCID 705561-Phenyl-1,3,8-triazaspiro(4.5)decan-4-oneHCID 14031282HCID 14031282, compound

Product 1

HCID 131715390HCID 131715390, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 6.0 g (0.032 mole) of the title compound of Example 11 and 7.45 g (0.032 mole) of 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one in 150 mL of ethanol was heated to reflux under argon for 48 hours. The solvent was evaporated and the residue chromatographed on 500 g of silica gel (dry column) eluting with the lower phase of a mixture prepared by shaking 90 parts CHCl3, 30 parts CH3OH, 10 parts H2O, and 6 parts acetic acid. The fractions containing free base of the title compound were concentrated at 35°-50° C. on a rotary evaporator. The residue was dissolved in 500 mL of methylene chloride and neutralized to pH 10-11 with ice cold 1:1 NH4OH:H2O. The layers were separated and the organic phase was dried over Na2SO4 and concentrated. The residual solid was washed with hot ethanol and filtered. A sample of the free base, recrystallized from ethanol, had mp 183°-185° C. For the preparation of the HCl salt, the filter cake was suspended in 100 mL of ethanol and treated with about 10 mL of 5N HCl in ether. The solution was concentrated and allowed to cool, whereupon the hydrochloride salt of the title compound precipitated out. Two crops were collected, affording a total of 5.85 g of the hydrochloride salt of the title compound after drying at 100° C./1.0 mm overnight.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under argon for 48 hours
  3. customThe solvent was evaporated
  4. customthe residue chromatographed on 500 g of silica gel (dry column)
  5. washeluting with the lower phase of a mixture
  6. customprepared

Sources & evidence

ORD record
ord-2be895df3e194c5cb8778e5b15d47c65
Source dataset
uspto-grants-1987_11
Patent number
US04707484

Reaction notes

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