1,2-Dichloroethane → HCID 67459994, compound

HRID 1804470Notes

Reaction equation

HRID 1804470 reaction equation
[C:1]([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)([CH3:4])([CH3:3])[CH3:2].C1C=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>[C:1]([C:5]1[C:6]([C:16]2[O:18][N:45]=[C:44]([C:46]3[CH:47]=[CH:48][C:49]([CH2:50][N:51]4[CH2:52][CH:53]([C:55]([O:57][C:58]([CH3:59])([CH3:61])[CH3:60])=[O:56])[CH2:54]4)=[CH:62][CH:63]=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)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58504340HCID 58504340, compoundHCID 58537179HCID 58537179, compound

Product 1

HCID 67459994HCID 67459994, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-tert-butyl-5-phenylisoxazole-3-carboxylic acid (25 mg, 0.102 mmol), HOBt (28.1 mg, 0.183 mmol), and diisopropylethylamine (0.071 mL, 0.408 mmol) in acetonitrile (1 mL) was added EDC (45.9 mg, 0.240 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 31.1 mg, 0.102 mmol). The reaction mixture was stirred at 80° C. for 5 h. The reaction mixture was concentrated, and 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 afforded tert-butyl 1-(4-(5-(4-tert-butyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)-azetidine-3-carboxylate.

Workup

  1. concentrationThe reaction mixture was concentrated
  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-3f06549365fd45bfbe96477bfcced35d
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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