1,2-Dichloroethane → HCID 59143428, compound

HRID 1920726Notes

Reaction equation

HRID 1920726 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH:24]([C:28]1[CH:32]=[C:31]([NH:33][C:34]([N:36]2[CH2:42][CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[O:35])[O:30][N:29]=1)([CH2:26][CH3:27])[CH3:25]>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[CH:24]([C:28]1[CH:32]=[C:31]([NH:33][C:34]([N:36]2[CH2:42][CH2:41][CH2:40][N:39]([C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[O:9])[CH2:38][CH2:37]2)=[O:35])[O:30][N:29]=1)([CH2:26][CH3:27])[CH3:25]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 219302Oxane-4-carboxylic acidHCID 59143414HCID 59143414, compound

Product 1

HCID 59143428HCID 59143428, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Tetrahydropyran-carboxylic acid (66 mg; 0.50 mmol; 1.1 equiv.), HOBt (81 mg; 0.6 mmol; 1.4 equiv.) and EDC (115 mg; 0.6 mmol; 1.4 equiv.) were combined in 2 mL anhydrous DMF. After 15 minutes [1,4]Diazepane-1-carboxylic acid (3-sec-butyl-isoxazol-5-yl)-amide from above (117 mg; 0.44 mmol; 1.0 equiv.) was added, followed by 2 mg of DMAP (catalytic). The mixture was left stirring overnight. Water was added to the reaction mixture and it was extracted with EtOAc. The organic layer was washed with water once then saturated aqueous NaHCO3 solution, saturated aqueous NH4Cl solution, then brine. The organics were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using 2.5% MeOH/DCM mixtures as eluent, then switched to 10% MeOH/DCM. Solvents were removed from the enriched fractions and 61 mg of 4-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (3-sec-butyl-isoxazol-5-yl)-amide was obtained (36% yield) as a light yellow solid.

Workup

  1. waitThe mixture was left
  2. extractionwas extracted with EtOAc
  3. washThe organic layer was washed with water once
  4. dry with materialThe organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography
  8. customSolvents were removed from the enriched fractions

Sources & evidence

ORD record
ord-48230c63d55547959ede10330dd43935
Source dataset
uspto-grants-2012_05
Patent number
US08173638B2

Reaction notes

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