Lithium Hydroxide → HCID 58714536, compound

HRID 1242602Notes

Reaction equation

HRID 1242602 reaction equation
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[C:17]2[O:21][N:20]=[C:19]([C:22](OCC)=[O:23])[N:18]=2)=[O:8])=[CH:3][CH:2]=1.[Li+].[OH-].CCN=C=[N:39][CH2:40][CH2:41][CH2:42][N:43]([CH3:45])[CH3:44].Cl.CN(C)CCCN>C1COCC1.C(Cl)Cl.O>[C:1]1([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:2]=[CH:3][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[C:17]2[O:21][N:20]=[C:19]([C:22]([NH:39][CH2:40][CH2:41][CH2:42][N:43]([CH3:45])[CH3:44])=[O:23])[N:18]=2)=[O:8])=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 7993N,N-Dimethyl-1,3-propanediamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58714524HCID 58714524, compound

Product 1

HCID 58714536HCID 58714536, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 5-[(2S,4EZ)-1-([1,1′-biphenyl]-4-ylcarbonyl)-4-(methoxyimino)pyrrolidinyl]-1,2,4-oxadiazole-3-carboxylate (187 mg, 0.43 mmol, Example 57) was dissolved in 3:1 THF:water (10 mL) and stirred. LiOH (20 mg, 0.47 mmol, 1.1 eq) was added and the mixture stirred for 2 hours at room temperature. THF was removed in vacuo, the residue diluted in water and the solution acidified with 6N HCl (2 drops, pH=5). The aqueous phase was extracted with DCM (2×10 mL). The organic phase was dried with magnesium sulfate and the solvent removed in vacuo to give the acid derivative (165 mg, 94%) as a yellow oil. This crude intermediate (102 mg, 0.25 mmol) was dissolved in DCM (5 mL) and cooled to 0° C. EDC.HCl (53 mg, 0.28 mmol, 1.1 eq) was added in one portion and the mixture stirred for 10 minutes. N′,N′-dimethyl-1,3-propanediamine (35 mg, 0.28 mmol, 1.1 eq) was added and the solution stirred at room temperature over night. The mixture was then washed with 10% aqueous citric acid (2×5 mL). The separation was not good due to the partial solubility of the compound in water. Organic solvent was removed in vacuo and the residue was purified by semi-prep-LC to give the title compound in 56% yield (93% purity by HPLC).

Workup

  1. customTHF was removed in vacuo
  2. additionthe residue diluted in water
  3. extractionThe aqueous phase was extracted with DCM (2×10 mL)
  4. dry with materialThe organic phase was dried with magnesium sulfate
  5. customthe solvent removed in vacuo
  6. customto give the acid derivative (165 mg, 94%) as a yellow oil
  7. temperaturecooled to 0° C
  8. stirringthe mixture stirred for 10 minutes
  9. stirringthe solution stirred at room temperature over night
  10. washThe mixture was then washed with 10% aqueous citric acid (2×5 mL)
  11. customThe separation
  12. customOrganic solvent was removed in vacuo
  13. customthe residue was purified by semi-prep-LC

Sources & evidence

ORD record
ord-48dbddddae0e44e1b686f8743f46852c
Source dataset
uspto-grants-2006_10
Patent number
US07115639B2

Reaction notes

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