Potassium Iodide → N-Cyclopropyl-2-fluoro-4-methyl-5-{3-[(1-{2-[2-(methylamino)ethoxy]phenyl}cyclopropyl)amino]-2-oxopyrazin-1(2H)-yl}benzamide

HRID 2070823Notes

Reaction equation

HRID 2070823 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:35])[N:17]([C:21]3[C:22]([CH3:34])=[CH:23][C:24]([F:33])=[C:25]([CH:32]=3)[C:26]([NH:28][CH:29]3[CH2:31][CH2:30]3)=[O:27])[CH:18]=[CH:19][N:20]=2)[CH2:13][CH2:12]1.[CH3:36][NH2:37].[I-].[K+]>O.O1CCOCC1>[CH:29]1([NH:28][C:26](=[O:27])[C:25]2[CH:32]=[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:37][CH3:36])[CH2:13][CH2:12]4)[C:16]3=[O:35])[C:22]([CH3:34])=[CH:23][C:24]=2[F:33])[CH2:31][CH2:30]1

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 6329MethylamineHCID 666892205-[3-({1-[2-(2-Chloroethoxy)phenyl]cyclopropyl}amino)-2-oxopyrazin-1(2H)-yl]-N-cyclopropyl-2-fluoro-4-methylbenzamide

Product 1

HCID 66690397N-Cyclopropyl-2-fluoro-4-methyl-5-{3-[(1-{2-[2-(methylamino)ethoxy]phenyl}cyclopropyl)amino]-2-oxopyrazin-1(2H)-yl}benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-[3-({1-[2-(2-chloroethoxy)phenyl]cyclopropyl}amino)-2-oxopyrazin-1(2H)-yl]-N-cyclopropyl-2-fluoro-4-methylbenzamide (Example 318h, 100 mg) and methylamine, 40% by wt solution in water (0.1 mL) in dioxane (1 mL) was added potassium iodide (33.4 mg). The reaction mixture was stirred at room temperature overnight, then heated at 40° C. overnight. The reaction was heated at 50° C. for 48 h. Purification by preparative HPLC (Phenomenex Gemini, eluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia, followed by Xbridge column eluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia) gave the title compound as a solid (17 mg).

Workup

  1. temperatureheated at 40° C. overnight
  2. temperatureThe reaction was heated at 50° C. for 48 h
  3. customPurification by preparative HPLC (Phenomenex Gemini
  4. washeluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia
  5. washeluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia)

Sources & evidence

ORD record
ord-d673257e29f84f55abd49852a145b1f9
Source dataset
uspto-grants-2012_10
Patent number
US08299246B2

Reaction notes

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