1,2-Dichloroethane → HCID 67459036, compound

HRID 1804478Notes

Reaction equation

HRID 1804478 reaction equation
[F:1][C:2]([C:5]1[C:6]([C:16]([OH:18])=O)=[N:7][O:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([F:4])[CH3:3].[CH:19]1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl.O/[N:43]=[C:44](/[C:46]1[CH:63]=[CH:62][C:49]([CH2:50][N:51]2[CH2:54][CH:53]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:52]2)=[CH:48][CH:47]=1)\[NH2:45]>C(#N)C>[F:4][C:2]([C:5]1[C:6]([C:16]2[O:18][N:45]=[C:44]([C:46]3[CH:63]=[CH:62][C:49]([CH2:50][N:51]4[CH2:54][CH:53]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:52]4)=[CH:48][CH:47]=3)[N:43]=2)=[N:7][O:8][C:9]=1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([F:1])[CH2:3][CH3:19]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58504340HCID 58504340, compoundHCID 58537182HCID 58537182, compound

Product 1

HCID 67459036HCID 67459036, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-(1,1-difluoroethyl)-5-phenylisoxazole-3-carboxylic acid (58.7 mg, 0.232 mmol), HOBt (64.0 mg, 0.418 mmol), and diisopropylethylamine (0.162 mL, 0.928 mmol) in acetonitrile (2 mL) was added EDC (105 mg, 0.545 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 70.8 mg, 0.232 mmol). The reaction mixture was stirred at 80° C. for 2 h and then concentrated. The residue was diluted with ethyl acetate (3 mL), washed with a saturated aqueous solution of sodium bicarbonate (1 mL), washed with water (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by preparative HPLC gave tert-butyl 1-(4-(5-(4-(1,1-difluoropropyl)-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate.

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with ethyl acetate (3 mL)
  3. washwashed with a saturated aqueous solution of sodium bicarbonate (1 mL)
  4. washwashed with water (1 mL)
  5. washwashed with brine (1 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration
  8. customfollowed by purification by preparative HPLC

Sources & evidence

ORD record
ord-b8589a8e052942159e122857b1b99217
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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