Sodium t-butoxide → HCID 178426486, compound

HRID 707433Notes

Reaction equation

HRID 707433 reaction equation
Cl[C:2]1[C:3]([C:8]([CH3:27])([CH3:26])[C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][C@@H:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=3)[CH2:14][CH2:13]2)=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1.CC(C)([O-])C.[Na+]>CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC(OC)(C)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[CH3:26][C:8]1([CH3:27])[C:3]2[C:2](=[N:7][CH:6]=[CH:5][N:4]=2)[N:11]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=3)[CH2:14][CH2:13]2)[C:9]1=[O:10]

Participants

5

Reactant 2

HCID 23676156Sodium t-butoxideHCID 178426491HCID 178426491, compound

Product 1

HCID 178426486HCID 178426486, compoundYield 32.9%

Reagents, catalysts & solvents 2

HCID 66572931HCID 66572931, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a glass microwave reaction vessel was added 2-(3-chloropyrazin-2-yl)-2-methyl-N-(cis-4-((5-methylpyridin-2-yl)amino)cyclohexyl)propanamide (0.1050 g, 0.271 mmol), RuPhos Precatalyst (0.012 g, 0.016 mmol, Strem Chemicals), and sodium tert-butoxide (0.052 g, 0.541 mmol, Sigma-Aldrich Chemical Company, Inc.) in dry dioxane (0.271 ml) to stir at 90° C. for 17 h. Solvent was evaporated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (25 g), eluting with a gradient of 10% to 100% EtOAc in hexane, to provide the title compound (0.0313 g, 0.089 mmol, 32.9% yield). LCMS showed product peak at 1.526 min (m+1=352.1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33 (s, 6 H) 1.52 (d, J=11.93 Hz, 2 H) 1.64 (t, J=13.60 Hz, 2 H) 1.98-2.14 (m, 5 H) 2.58 (d, J=10.37 Hz, 2 H) 3.91 (br. s., 1 H) 4.16-4.30 (m, 1 H) 6.16 (br. s., 1 H) 6.58 (d, J=8.41 Hz, 1 H) 7.24 (dd, J=8.31, 2.05 Hz, 1 H) 7.81 (s, 1 H) 8.15 (d, J=3.13 Hz, 1 H) 8.16-8.21 (m, 1 H)

Workup

  1. customTo a glass microwave reaction vessel
  2. customSolvent was evaporated in vacuo
  3. customchromatographed through a Biotage SNAP HP-silica gel column (25 g)
  4. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-73ba57892af94b6cba55984349f3a7f1
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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