1,2-Dichloroethane → HCID 58537189, compound

HRID 1804503Notes

Reaction equation

HRID 1804503 reaction equation
[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]([OH:12])=O)[C:6]=1[CH2:13][CH2:14][CH3:15])[CH:2]([CH3:4])[CH3:3].[CH2:16]([C:20]1[C:21]([C:28]([OH:30])=O)=[N:22][O:23][C:24]=1[CH2:25][CH2:26][CH3:27])[CH:17]([CH3:19])[CH3:18].O/[N:32]=[C:33](/[C:35]1[CH:52]=[CH:51][C:38]([CH2:39][N:40]2[CH2:43][CH:42]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:41]2)=[CH:37][CH:36]=1)\[NH2:34].C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl>CN(C=O)C>[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]2[O:12][N:34]=[C:33]([C:35]3[CH:36]=[CH:37][C:38]([CH2:39][N:40]4[CH2:41][CH:42]([C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])[CH2:43]4)=[CH:51][CH:52]=3)[N:32]=2)[C:6]=1[CH2:13][CH2:14][CH3:15])[CH:2]([CH3:3])[CH3:4].[CH2:16]([C:20]1[C:21]([C:28]2[O:30][N:34]=[C:33]([C:35]3[CH:36]=[CH:37][C:38]([CH2:39][N:40]4[CH2:41][CH:42]([C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])[CH2:43]4)=[CH:51][CH:52]=3)[N:32]=2)=[N:22][O:23][C:24]=1[CH2:25][CH2:26][CH3:27])[CH:17]([CH3:18])[CH3:19]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58504340HCID 58504340, compoundHCID 58537221HCID 58537221, compoundHCID 58537233HCID 58537233, compound

Product 2

HCID 58537189HCID 58537189, compoundYield 66.6%HCID 58537195HCID 58537195, compoundYield 66.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 5-isobutyl-4-propylisoxazole-3-carboxylic acid, and 4-isobutyl-5-propylisoxazole-3-carboxylic acid (42.26 mg, 0.2 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (61.1 mg, 0.200 mmol), HOBt (38.3 mg, 0.250 mmol), diisopropylethylamine (0.070 mL, 0.400 mmol) and EDC (47.9 mg, 0.250 mmol) in DMF (1 mL) was stirred at rt for 18 hr. DMF (1 mL) was added and the reaction mixture was warmed to 50° C. for 8 hr. The reaction mixture was partitioned between EtOAc (30 ml) and saturated sodium bicarbonate solution (30 ml). The organic layer was washed with water (2×30 ml) and brine (30 ml). After drying (MgSO4) and filtration, the organic layer was concentrated to afford an oil that was chromatographed on a 4 gm Isco silica gel cartridge, eluting with a 0-100% EtOAc/Hex gradient. The pure fractions were concentrated to afford a mixture of tert-butyl 1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (32 mg, 0.067 mmol, 66.6% yield) and tert-butyl 1-(4-(5-(4-isobutyl-5-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (32 mg, 0.067 mmol, 66.6% yield) as a colorless oil. HPLC retention time=1.89 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient.

Workup

  1. temperaturethe reaction mixture was warmed to 50° C. for 8 hr
  2. customThe reaction mixture was partitioned between EtOAc (30 ml) and saturated sodium bicarbonate solution (30 ml)
  3. washThe organic layer was washed with water (2×30 ml) and brine (30 ml)
  4. customAfter drying
  5. filtration(MgSO4) and filtration
  6. concentrationthe organic layer was concentrated
  7. customto afford an oil that
  8. customwas chromatographed on a 4 gm Isco silica gel cartridge
  9. washeluting with a 0-100% EtOAc/Hex gradient
  10. concentrationThe pure fractions were concentrated
  11. customto afford

Sources & evidence

ORD record
ord-9b36985d526f45f89c689d54dd4891b3
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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