Ethylacetate methanol → HCID 46911175, compound

HRID 545093Notes

Reaction equation

HRID 545093 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[C:4]([C:11]2[N:16]=[C:15]3[N:17]=[CH:18][CH:19]=[C:20]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][N:23]=4)[C:14]3=[N:13][CH:12]=2)=[N:5][CH:6]=[C:7]([CH:10]=1)[C:8]#[N:9].CO.CC[O:38]C(C)=O>OS(O)(=O)=O>[F:33][C:2]([F:1])([F:32])[C:3]1[C:4]([C:11]2[N:16]=[C:15]3[N:17]=[CH:18][CH:19]=[C:20]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:30])([F:29])[F:31])=[CH:24][N:23]=4)[C:14]3=[N:13][CH:12]=2)=[N:5][CH:6]=[C:7]([CH:10]=1)[C:8]([NH2:9])=[O:38]

Participants

4

Reactant 2

HCID 21584119Ethylacetate methanolHCID 49863890HCID 49863890, compound

Product 1

HCID 46911175HCID 46911175, compound

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
25 °C

Procedure

Dissolve 5-(trifluoromethyl)-6-(8-(5-(trifluoromethyl)pyridin-2-ylamino)pyrido[2,3-b]pyrazin-3-yl)nicotinonitrile (25 mg, 0.0542 mmol) in 1 mL of conc. H2SO4 and stir at 25° C. for 20 hours under N2 atmosphere. Monitor the reaction by TLC (1% MeOH/EtOAc) and LC/MS for the disappearance of starting material. Quench the reaction mixture with ice (5 g), adjust the pH to 9.0 using 10.0 N aq. NaOH, extract the aq. layer with EtOAc (3×5.0 ml) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum. Purify by column chromatography using 1% MeOH/EtOAc as eluent to afford the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 9.4 (s, 1H), 9.36 (d, 1H, J=0.6 Hz), 9.18 (s, 1H), 9.09 (d, 1H, J=1.4 Hz), 8.95 (d, 1H, J=1.3 Hz), 8.73 (s, 1H), 8.70(d, 1H, J=0.5 Hz), 7.89 (dd, 1H), 7.13 (d, 1H, J=2.2 Hz). MS=480.01 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.

Workup

  1. customQuench the reaction mixture with ice (5 g)
  2. extractionextract the aq. layer with EtOAc (3×5.0 ml)
  3. customdry
  4. filtrationFilter the dried
  5. extractionextract
  6. concentrationconcentrate under vacuum
  7. customPurify by column chromatography

Sources & evidence

ORD record
ord-7fc72b3d8e014beeae16113808d3f4c9
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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