Dimethylformamide → 5-[3-[4-({4-[(1,1-Dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-5-oxo-1,2,4-oxadiazol-4-yl]-2-fluorobenzonitrile trifluoroacetate

HRID 1663493Notes

Reaction equation

HRID 1663493 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].Br[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:26]([NH:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:36]4[CH2:41][CH2:40][S:39](=[O:43])(=[O:42])[CH2:38][CH2:37]4)=[CH:31][CH:30]=3)=[N:25][O:24][N:23]=2)[CH:12]=[CH:13][C:14]=1[F:15].[CH3:44][N:45](C)C=O>C(#N)C.O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[O:42]=[S:39]1(=[O:43])[CH2:40][CH2:41][N:36]([CH2:35][C:32]2[CH:33]=[CH:34][C:29]([CH2:28][NH:27][C:26]3[C:22]([C:17]4[N:16]([C:11]5[CH:12]=[CH:13][C:14]([F:15])=[C:9]([CH:10]=5)[C:44]#[N:45])[C:20](=[O:21])[O:19][N:18]=4)=[N:23][O:24][N:25]=3)=[CH:30][CH:31]=2)[CH2:37][CH2:38]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 674350044-(3-Bromo-4-fluorophenyl)-3-[4-({4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5(4H)-one trifluoroacetate

Product 1

HCID 674381925-[3-[4-({4-[(1,1-Dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-5-oxo-1,2,4-oxadiazol-4-yl]-2-fluorobenzonitrile trifluoroacetate

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 4-(3-bromo-4-fluorophenyl)-3-[4-({4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5(4H)-one trifluoroacetate (10 mg, 14 μmol), zinc cyanide (5 mg, 43 μmol), and tetrakis(triphenylphosphine)palladium(0) (8 mg, 7 μmol) in N,N-dimethylformamide (0.25 mL) was heated in the microwave at 150° C. for 5 min. The reaction mixture was diluted with 3:1 acetonitrile/water (2 mL), filtered, and purified by preparative LCMS to give the intermediate 5-[3-[4-({4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-5-oxo-1,2,4-oxadiazol-4(5H)-yl]-2-fluorobenzonitrile trifluoroacetate. This material was diluted with ethanol (1 mL), treated with 2.0 M sodium hydroxide in water (0.1 mL), and stirred for 45 min. The reaction mixture was quenched with acetic acid (50 μL, 0.9 mmol), filtered, and purified by preparative LCMS to give the desired product (1 mg, 11%). LCMS for C22H23FN7O4S (M+H)+: m/z=500.0.

Workup

  1. filtrationfiltered
  2. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-9c67206b22414f6182805e33d8183f73
Source dataset
uspto-grants-2011_10
Patent number
US08034953B2

Reaction notes

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