Methanesulfonyl chloride → N-((2-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-N-(2-methoxyethyl)methanesulfonamide

HRID 1026825Notes

Reaction equation

HRID 1026825 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]([CH3:35])[C:26]([CH2:29][NH:30][CH2:31][CH2:32][O:33][CH3:34])=[CH:27][N:28]=5)[S:23][C:16]=34)=[C:10]([F:36])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:37][S:38](Cl)(=[O:40])=[O:39].CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]([CH3:35])[C:26]([CH2:29][N:30]([CH2:31][CH2:32][O:33][CH3:34])[S:38]([CH3:37])(=[O:40])=[O:39])=[CH:27][N:28]=5)[S:23][C:16]=34)=[C:10]([F:36])[CH:9]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 252699041-Cyclopropyl-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

Product 1

HCID 44229638N-((2-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-N-(2-methoxyethyl)methanesulfonamideYield 48.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of the amine 348 (61 mg, 0.119 mmol) in DCM (5 ml) was added methanesulfonyl chloride (20.53 mg, 1.5 eq, 0.179 mmol) and iPr2NEt (46.3 mg, 3 eq, 0.358 mmol) and the reaction mixture was stirred at RT for 3 hours. The mixture was diluted with EtOAc then washed with saturated NH4Cl solution, saturated NaHCO3 solution and brine. The organic phase was collected, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (eluent 25% MeOH in EtOAc) to afford the desired compound 349 as a pale yellow solid (34 mg, 48%). 1H NMR (d6 DMSO) 8.27 (s, 1H), 8.10 (d, J=5.48 Hz, 1H), 7.53 (s, 1H), 7.25 (m, 1H), 6.95 (t, J=9.0 Hz, 1H), 6.76 (m, 1H), 6.71 (s, 1H), 6.24 (d, J=5.48 Hz, 1H), 6.14 (s, 1H), 4.06 (s, 2H), 3.49 (s, 3H), 2.72 (s, 3H), 2.63 (s, 3H), 2.12 (m, 3H), 0.23 (m, 2H), 0.00 (s, 2H).

Workup

  1. washthen washed with saturated NH4Cl solution, saturated NaHCO3 solution and brine
  2. customThe organic phase was collected
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (eluent 25% MeOH in EtOAc)

Sources & evidence

ORD record
ord-3d853871838944659ddb878dd749d399
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

Loading…