Sodium Acetate → HCID 58504354, compound

HRID 1941895Notes

Reaction equation

HRID 1941895 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15]/[N:16]=[C:17](/[C:19]1[CH:33]=[CH:32][C:22]([CH2:23][N:24]2[CH2:27][CH:26]([C:28]([O:30][CH3:31])=[O:29])[CH2:25]2)=[CH:21][CH:20]=1)\[NH2:18])=O.C([O-])(=O)C.[Na+]>CCO.O>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]1[O:15][N:16]=[C:17]([C:19]2[CH:33]=[CH:32][C:22]([CH2:23][N:24]3[CH2:27][CH:26]([C:28]([O:30][CH3:31])=[O:29])[CH2:25]3)=[CH:21][CH:20]=2)[N:18]=1

Participants

5

Reactant 2

HCID 517045Sodium AcetateHCID 58504345HCID 58504345, compound

Product 1

HCID 58504354HCID 58504354, compoundYield 71.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of (Z)-methyl 1-(4-(N′-(5-amino-1-phenyl-1H-pyrazole-4-carbonyloxy)carbamimidoyl)benzyl)azetidine-3-carboxylate (102 mg, 0.227 mmol) in EtOH (3 mL) was added sodium acetate (37.3 mg, 0.455 mmol) as a solution in water (1 mL). The mixture was heated to 90° C. for 3 hr. The reaction mixture was transferred to a microwave vial and was then heated to 120° C. for 30 minutes. The reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL). The aqueous layer was extracted with EtOAc (15 mL) and the combined organic layers were dried (MgSO4) and concentrated to afford an oil that was chromatographed on a 12 gm Isco silica gel cartridge, eluting with a 0-100% EtOAc/hexane gradient. The pure fractions were concentrated to afford methyl 1-(4-(5-(5-amino-1-phenyl-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (70 mg, 0.163 mmol) as a colorless oil. HPLC retention time=1.35 (ethyl ester-1.42) minutes (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS:(M+H)=431.23 (ethyl ester-445.25). (The product is a mixture of methyl ester and ethyl ester due to partial transesterification during the reaction. The mixture was carried on through the sequence.)

Workup

  1. temperaturewas then heated to 120° C. for 30 minutes
  2. customThe reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (15 mL)
  4. dry with materialthe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated
  6. customto afford an oil that
  7. customwas chromatographed on a 12 gm Isco silica gel cartridge
  8. washeluting with a 0-100% EtOAc/hexane gradient
  9. concentrationThe pure fractions were concentrated

Sources & evidence

ORD record
ord-4199751dc38e42fabbaccd95acd7f3fd
Source dataset
uspto-grants-2013_03
Patent number
US08389509B2

Reaction notes

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