Sodium t-butoxide → HCID 178426487, compound

HRID 707317Notes

Reaction equation

HRID 707317 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 178426492HCID 178426492, compound

Product 1

HCID 178426487HCID 178426487, compoundYield 9.2%

Reagents, catalysts & solvents 2

HCID 66572931HCID 66572931, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a glass microwave vial was added 2-(3-chloropyrazin-2-yl)-2-methyl-N-(trans-4-((5-methylpyridin-2-yl)amino)cyclohexyl)propanamide (0.2148 g, 0.554 mmol), RuPhos precatalyst (0.024 g, 0.033 mmol), and sodium tert-butoxide (0.106 g, 1.107 mmol) in dry dioxane (0.554 ml). The mixture was sealed and stirred at 80° C. for 3 hours. The mixture was allowed to cool to room temperature then 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 0% to 5% methanol in dichloromethane, to provide 7,7-dimethyl-5-(trans-4-((5-methylpyridin-2-yl)amino)cyclohexyl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (0.0178 g, 0.051 mmol, 9.15% yield). M+1: 324. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 6 H) 1.50-1.72 (m, 3 H) 2.18 (s, 3 H) 2.23-2.35 (m, 2 H) 3.37-3.48 (m, 2 H) 4.36-4.46 (m, 1 H) 4.71-4.77 (m, 1 H) 5.27 (quin, J=8.90 Hz, 1 H) 6.26 (d, J=8.00 Hz, 1 H) 6.92-6.99 (m, 1 H) 7.42 (d, J=5.87 Hz, 1 H) 7.90-7.97 (m, 1 H) 8.15-8.20 (m, 1 H)

Workup

  1. customThe mixture was sealed
  2. temperatureto cool to room temperature
  3. customchromatographed through a Biotage SNAP HP-silica gel column (25 g)
  4. washeluting with a gradient of 0% to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-1c22b59c4cb4491bb2e16e4b47d3686d
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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