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 1663495Notes

Reaction equation

HRID 1663495 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 mmol) 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-0f1b83fd44a542d4aa5baedb93942b90
Source dataset
uspto-grants-2011_10
Patent number
US08034953B2

Reaction notes

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