1,2-Dichloroethane → HCID 58537214, compound

HRID 1804497Notes

Reaction equation

HRID 1804497 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:7][O:8][C:9]=1[C:10]([OH:12])=O)=[O:4].O/[N:20]=[C:21](/[C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:31][CH:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]2)=[CH:25][CH:24]=1)\[NH2:22].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:1][NH:2][C:3]([C:5]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:7][O:8][C:9]=1[C:10]1[O:12][N:22]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([CH2:27][N:28]3[CH2:29][CH:30]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:31]3)=[CH:39][CH:40]=2)[N:20]=1)=[O:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58504340HCID 58504340, compoundHCID 67454912HCID 67454912, compound

Product 1

HCID 58537214HCID 58537214, compoundYield 43.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(methylcarbamoyl)-3-phenylisoxazole-5-carboxylic acid (32 mg, 0.130 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int.1, (39.7 mg, 0.130 mmol), HOBT (31.8 mg, 0.208 mmol), EDC (58.5 mg, 0.305 mmol) and diisopropylethylamine (0.091 mL, 0.520 mmol) in DMF (1 mL) was stirred at rt for 18 hr. After warming to 60° C. for 3 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 a yellow oil that was chromatographed on a 4 gm Isco silica gel cartridge, eluting with a 0-90% EtOAc/Hex gradient. The essentially pure fractions containing product were concentrated to afford tert-butyl 1-(4-(5-(4-(methylcarbamoyl)-3-phenylisoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (29 mg, 0.056 mmol, 43.3% yield) as a colorless glassy solid. HPLC retention time=1.50 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient. MS: (M+H)=516.27.

Workup

  1. temperatureAfter warming to 60° C. for 3 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 to a yellow oil that
  7. customwas chromatographed on a 4 gm Isco silica gel cartridge
  8. washeluting with a 0-90% EtOAc/Hex gradient
  9. additionThe essentially pure fractions containing product
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-95bb72e44c53488a9246c5c4015337ec
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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