(S)-3-(4-(7-Iodo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one → (S)-3-(4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-carbonitrile

HRID 525379Notes

Reaction equation

HRID 525379 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C@@H:21]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[C:20]([CH3:29])([CH3:28])[O:19][C:18]4=[O:30])=[CH:13][CH:12]=3)=[N:9][N:10]=[C:4]2[CH:3]=1.[C:31]([Zn]C#N)#[N:32]>CN(C=O)C.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>[CH3:29][C:20]1([CH3:28])[O:19][C:18](=[O:30])[N:17]([C:14]2[CH:13]=[CH:12][C:11]([C:8]3[N:5]4[CH:6]=[CH:7][C:2]([C:31]#[N:32])=[CH:3][C:4]4=[N:10][N:9]=3)=[CH:16][CH:15]=2)[C@H:21]1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 2

HCID 89815193(S)-3-(4-(7-Iodo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-oneHCID 178514179HCID 178514179, compound

Product 1

HCID 89815474(S)-3-(4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-carbonitrileYield 35.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a 2 mL sealable tube were added (S)-3-(4-(7-iodo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (70 mg, 0.137 mmol), dicyanozinc (16.11 mg, 0.137 mmol, commercially available from Sigma-Aldrich, Milwaukee, Wis.) and Pd(Ph3P)4 (15.85 mg, 0.014 mmol, commercially available from Sigma-Aldrich, Milwaukee, Wis.) in DMF (457 μL). The mixture was purged with nitrogen for 5 minutes and then the tube was sealed. The vessel was heated to 85° C. in a microwave oven for 1 hour. LC-MS indicated complete conversion to the desired product. The final reaction mixture was passed through a syringe filter, and the material thus obtained was purified by reverse-phase preparative HPLC using 0.1% TFA in ACN/H2O, gradient 15% to 90% over 20 minutes to provide (S)-3-(4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-carbonitrile (20 mg, 0.049 mmol, 35.6% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 8.71 (t, J=1.37 Hz, 1H), 8.66 (dd, J=1.17, 7.34 Hz, 1H), 7.84-7.90 (m, 2H), 7.72-7.78 (m, 2H), 7.37-7.44 (m, 2H), 7.28-7.37 (m, 3H), 7.22 (dd, J=1.56, 7.34 Hz, 1H), 5.56 (s, 1H), 1.67 (s, 3H), 0.94 (s, 3H). m/z (ESI) 410.2 (M+H)+.

Workup

  1. customThe mixture was purged with nitrogen for 5 minutes
  2. customthe tube was sealed
  3. customThe final reaction mixture
  4. customwas passed through a syringe
  5. filtrationfilter
  6. customthe material thus obtained
  7. customwas purified by reverse-phase preparative HPLC
  8. customover 20 minutes

Sources & evidence

ORD record
ord-8023368e536042ba9368e93af448b8f9
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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