Phosphorus pentachloride → 4-(3-bromo-4-fluorophenyl)-3-(4-{[4-(morpholin-4-ylmethyl)benzyl]amino}-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

HRID 1663491Notes

Reaction equation

HRID 1663491 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:10]=[C:11]([N:16]2[C:20](=[O:21])[O:19][N:18]=[C:17]2[C:22]2[C:23]([NH:27][C:28](=O)[C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[CH:31][CH:30]=3)=[N:24][O:25][N:26]=2)[CH:12]=[CH:13][C:14]=1[F:15].P(Cl)(Cl)(Cl)(Cl)Cl.C([BH3-])#N.[Na+]>C1C=CC=CC=1>[Br:8][C:9]1[CH:10]=[C:11]([N:16]2[C:20](=[O:21])[O:19][N:18]=[C:17]2[C:22]2[C:23]([NH:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]([CH2:35][N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)=[CH:33][CH:34]=3)=[N:24][O:25][N:26]=2)[CH:12]=[CH:13][C:14]=1[F:15]

Participants

5

Reactant 3

HCID 24819Phosphorus pentachlorideHCID 5003444Sodium cyanoborohydrideHCID 67436187N-{4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}-4-(morpholin-4-ylmethyl)benzamide trifluoroacetate

Product 1

HCID 674353974-(3-bromo-4-fluorophenyl)-3-(4-{[4-(morpholin-4-ylmethyl)benzyl]amino}-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of N-{4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}-4-(morpholin-4-ylmethyl)benzamide trifluoroacetate (60 mg, 91 μmol) in benzene (1.8 mL) was treated with phosphorus pentachloride (76 mg, 0.36 mmol) and stirred at reflux for 2.5 h. The reaction mixture was concentrated to a residue which was diluted with ethanol (1.4 mL), treated with sodium cyanoborohydride (17 mg, 0.27 mmol), and stirred for 2 h. The reaction mixture was quenched with acetic acid (50 μL) and purified by preparative LCMS to give the intermediate, 4-(3-bromo-4-fluorophenyl)-3-(4-{[4-(morpholin-4-ylmethyl)benzyl]amino}-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one. This material was diluted with ethanol (1 mL), treated with 2.0 M sodium hydroxide in water (0.2 mL, 4 mmol), and stirred for 45 min. The reaction mixture was purified by preparative LCMS to give the desired product (15 mg, 27%). LCMS for C21H23BrFN6O3 (M+H)+: m/z=505.0, 507.0.

Workup

  1. temperatureat reflux for 2.5 h
  2. concentrationThe reaction mixture was concentrated to a residue which
  3. additionwas diluted with ethanol (1.4 mL)
  4. stirringstirred for 2 h
  5. customThe reaction mixture was quenched with acetic acid (50 μL)
  6. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-10066f9f5f0f469a99a36c782a4f92d2
Source dataset
uspto-grants-2011_10
Patent number
US08034953B2

Reaction notes

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