Trifluoroacetic acid → 2-((3-(Methyl(methylsulfonyl)amino)-4-(4-morpholinylcarbonyl)phenyl)amino)-6-(4-morpholinyl)nicotinamide

HRID 2044103Notes

Reaction equation

HRID 2044103 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[C:14]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:29])=[O:28])[CH:13]=2)[N:3]=1.C(O)(C(F)(F)F)=O.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1>>[CH3:31][N:26]([S:27]([CH3:30])(=[O:29])=[O:28])[C:14]1[CH:13]=[C:12]([NH:11][C:4]2[N:3]=[C:2]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[CH:10]=[CH:9][C:5]=2[C:6]([NH2:8])=[O:7])[CH:17]=[CH:16][C:15]=1[C:18]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:19]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8083MorpholineHCID 574896506-Chloro-2-(3-(N-methylmethylsulfonamido)-4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 574896482-((3-(Methyl(methylsulfonyl)amino)-4-(4-morpholinylcarbonyl)phenyl)amino)-6-(4-morpholinyl)nicotinamideYield 38%

Procedure

A solution of 6-chloro-2-(3-(N-methylmethylsulfonamido)-4-(morpholine-4-carbonyl)phenylamino)nicotinamide (19 mg, 0.041 mmol) in morpholine (0.4 mL) in a sealed tube was stirred at 85° C. for 2 h. The morpholine was evaporated. The crude material was dissolved in 1 N aqueous HCl-MeOH (1:1, total 2 mL) and purified by reverse phase HPLC, using Shimadzu VP-ODS 20×100 mm column and eluting with 20% to 100% solvent B (10% MeOH-90% H2O-0.1% TFA) in solvent A (90% MeOH-10% H2O-0.1% TFA), to give the desired product as brown solid (11.7 mg, 38% yield) as bis-TFA salt. LCMS: (M+H)+=519.1. 1H NMR (400 MHz, methanol-d4) δ ppm 8.06 (1H, d, J=2.26 Hz), 7.90 (1H, d, J=8.78 Hz), 7.48 (1H, dd, J=8.41, 2.13 Hz), 7.26 (1H, d, J=8.53 Hz), 6.25 (1H, d, J=9.03 Hz), 3.70-3.93 (7H, m), 3.56-3.69 (7H, m), 3.41 (2H, t, J=4.64 Hz), 3.26 (3H, s), 3.06 (3H, s).

Workup

  1. customThe morpholine was evaporated
  2. dissolutionThe crude material was dissolved in 1 N aqueous HCl-MeOH (1:1, total 2 mL)
  3. custompurified by reverse phase HPLC
  4. washeluting with 20% to 100% solvent B (10% MeOH-90% H2O-0.1% TFA) in solvent A (90% MeOH-10% H2O-0.1% TFA)

Sources & evidence

ORD record
ord-aefb743a257d441fb6118ae9e749fc38
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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