Phosphorus pentachloride → 2-fluoro-5-[5-oxo-3-{4-[(pyridin-4-ylmethyl)amino]-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-4(5H)-yl}benzonitrile trifluoroacetate

HRID 82733Notes

Reaction equation

HRID 82733 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([C:10]1[CH:11]=[C:12]([N:17]2[C:21](=[O:22])[O:20][N:19]=[C:18]2[C:23]2[C:24]([NH:28][C:29](=O)[C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)=[N:25][O:26][N:27]=2)[CH:13]=[CH:14][C:15]=1[F:16])#[N:9].P(Cl)(Cl)(Cl)(Cl)Cl.C([BH3-])#N.[Na+]>N1C=CC=CC=1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:16][C:15]1[CH:14]=[CH:13][C:12]([N:17]2[C:21](=[O:22])[O:20][N:19]=[C:18]2[C:23]2[C:24]([NH:28][CH2:29][C:30]3[CH:31]=[CH:32][N:33]=[CH:34][CH:35]=3)=[N:25][O:26][N:27]=2)=[CH:11][C:10]=1[C:8]#[N:9]

Participants

5

Reactant 3

HCID 24819Phosphorus pentachlorideHCID 5003444Sodium cyanoborohydrideHCID 67435027N-{4-[4-(3-cyano-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}isonicotinamide trifluoroacetate

Product 1

HCID 674367542-fluoro-5-[5-oxo-3-{4-[(pyridin-4-ylmethyl)amino]-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-4(5H)-yl}benzonitrile trifluoroacetate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of N-{4-[4-(3-cyano-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}isonicotinamide trifluoroacetate (37 mg, 72 μmol) in pyridine (1.5 mL) at 0° C. was treated with phosphorus pentachloride (45 mg, 0.22 mmol) and stirred for 3 h. The reaction mixture was concentrated, diluted with ethanol (2.5 mL), treated with sodium cyanoborohydride (14 mg, 0.22 mmol), and stirred for 16 h. The reaction mixture was purified by preparative LCMS to give the intermediate 2-fluoro-5-[5-oxo-3-{4-[(pyridin-4-ylmethyl)amino]-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-4(5H)-yl}benzonitrile trifluoroacetate. This material was diluted with ethanol (1 mL), treated with 2.0 M sodium hydroxide in water (0.2 mL), and stirred for 45 min. Purification of the crude reaction mixture by preparative HPLC gave the desired product (8 mg, 24%). LCMS for C16H13FN7O2 (M+H)+: m/z=354.0.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethanol (2.5 mL)
  3. stirringstirred for 16 h
  4. customThe reaction mixture was purified by preparative LCMS

Sources & evidence

ORD record
ord-44434141a84f42d4900f7245ea4336b1
Source dataset
uspto-grants-2014_09
Patent number
US08846726B2

Reaction notes

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