Diethyl Ether → N-Cyclopropyl-4-methyl-3-(3-(1-(2-(2-(methylamino)ethoxy)phenyl)cyclopropylamino)-2-oxopyrazin-1(2H)-yl)benzamide

HRID 337176Notes

Reaction equation

HRID 337176 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1([NH:14][C:15]2[C:16](=[O:34])[N:17]([C:21]3[CH:22]=[C:23]([CH:30]=[CH:31][C:32]=3[CH3:33])[C:24]([NH:26][CH:27]3[CH2:29][CH2:28]3)=[O:25])[CH:18]=[CH:19][N:20]=2)[CH2:13][CH2:12]1.[CH3:35][NH2:36].C(OCC)C>O1CCOCC1.O>[CH:27]1([NH:26][C:24](=[O:25])[C:23]2[CH:30]=[CH:31][C:32]([CH3:33])=[C:21]([N:17]3[CH:18]=[CH:19][N:20]=[C:15]([NH:14][C:11]4([C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3][CH2:2][NH:36][CH3:35])[CH2:13][CH2:12]4)[C:16]3=[O:34])[CH:22]=2)[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 6329MethylamineHCID 66689514HCID 66689514, compound

Product 1

HCID 25143622N-Cyclopropyl-4-methyl-3-(3-(1-(2-(2-(methylamino)ethoxy)phenyl)cyclopropylamino)-2-oxopyrazin-1(2H)-yl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-(3-(1-(2-(2-Chloroethoxy)phenyl)cyclopropylamino)-2-oxopyrazin-1(2H)-yl)-N-cyclopropyl-4-methylbenzamide (Example 167e, 5.00 g) dissolved in dioxane (15 mL) was treated with methylamine (15 mL of a 40 wt % solution in water). The resulting suspension was stirred at 100° C. for 4 h in an autoclave. The solution was evaporated to dryness. The crude product was purified (SiO2 chromatography, eluting with a 5:1:94 (v/v) mixture of methanol:triethylamine:dichloromethane respectively). The product containing fractions were evaporated in vacuo and re-purified by RPHPLC (Xterra column, 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as mobile phase). The product containing fractions were combined and freeze dried to leave a solid. Trituration with diethyl ether followed by drying in vacuo overnight gave the title compound as a white powder (3.14 g).

Workup

  1. customThe solution was evaporated to dryness
  2. customThe crude product was purified (SiO2 chromatography
  3. washeluting with a 5:1:94 (v/v) mixture of methanol
  4. additionThe product containing fractions
  5. customwere evaporated in vacuo
  6. customre-purified by RPHPLC (Xterra column, 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as mobile phase)
  7. additionThe product containing fractions
  8. customfreeze dried
  9. customto leave a solid
  10. customby drying in vacuo overnight

Sources & evidence

ORD record
ord-a22d499115f24793a99c4f3155af7d32
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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