Phosphorus oxychloride → HCID 89815238, compound

HRID 525387Notes

Reaction equation

HRID 525387 reaction equation
[CH3:1][C:2]1([CH3:35])[O:6][C:5](=[O:7])[N:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][NH:15][C:16]([NH:18][C:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][N:27]=4)[N:22]=[CH:21][CH:20]=3)=O)[CH:9]=2)[C@H:3]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[N:22]1[C:23]2[C:28](=[N:27][CH:26]=[CH:25][CH:24]=2)[C:19]([NH:18][C:16]2[N:11]3[CH:12]=[CH:13][C:8]([N:4]4[C@@H:3]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[C:2]([CH3:35])([CH3:1])[O:6][C:5]4=[O:7])=[CH:9][C:10]3=[N:14][N:15]=2)=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 89813898HCID 89813898, compound

Product 1

HCID 89815238HCID 89815238, compoundYield 1.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of (S)-2-(4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)pyridin-2-yl)-N-(1,5-naphthyridin-4-yl)hydrazinecarboxamide (150 mg, 0.319 mmol) and POCl3 (292 μL, 3.19 mmol, commercially available from Sigma-Aldrich, Milwaukee, Wis.) in toluene (6.390 mL) was heated at 100° C. After stirring for 1 hour, an additional 1.5 mL of POCl3 was added to the reaction solution. After stirring for another 3 hours, the reaction mixture was concentrated under reduced pressure. The residue thus obtained was purified by reverse-phase preparative HPLC using 0.1% TFA in ACN/H2O, gradient 20% to 90% over 20 minutes to provide a material which was further purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 10% MeOH in DCM, to provide (S)-3-(3-((1,5-naphthyridin-4-yl)amino)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (2.41 mg, 5.34 μmol, 1.671% yield) as greenish solid. 1H NMR (500 MHz, DMSO-d6) δ 10.06-10.13 (m, 1H), 8.95-9.00 (m, 1H), 8.64 (br. s, 1H), 8.34-8.39 (m, 1H), 8.28 (d, J=6.09 Hz, 1H), 7.81-7.87 (m, 1H), 7.55 (d, J=9.62 Hz, 1H), 7.46-7.51 (m, 1H), 7.38-7.44 (m, 3H), 7.31-7.37 (m, 3H), 5.63 (s, 1H), 1.67 (s, 3H), 0.95 (s, 3H). m/z (ESI) 452.2 (M+H)+.

Workup

  1. stirringAfter stirring for another 3 hours
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe residue thus obtained
  4. customwas purified by reverse-phase preparative HPLC
  5. customover 20 minutes
  6. customto provide a material which
  7. customwas further purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  8. washeluting with a gradient of 0% to 10% MeOH in DCM

Sources & evidence

ORD record
ord-b3089eff498744a393bafbe9fd596b44
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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