Diisopropylethylamine → N-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-(piperidin-1-yl)imidazolidine-1-carboxamide

HRID 418692Notes

Reaction equation

HRID 418692 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[N:13]1([N:19]2[CH2:23][CH2:22][NH:21][C:20]2=[O:24])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[F:25][C:26]1[CH:27]=[C:28]([NH2:48])[CH:29]=[CH:30][C:31]=1[O:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]2[CH:39]=[C:40]([C:42]3[N:43]=[CH:44][N:45]([CH3:47])[CH:46]=3)[S:41][C:34]=12.CCN(C(C)C)C(C)C>C1COCC1.CO.C(Cl)Cl>[F:25][C:26]1[CH:27]=[C:28]([NH:48][C:2]([N:21]2[CH2:22][CH2:23][N:19]([N:13]3[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]3)[C:20]2=[O:24])=[O:4])[CH:29]=[CH:30][C:31]=1[O:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]2[CH:39]=[C:40]([C:42]3[N:43]=[CH:44][N:45]([CH3:47])[CH:46]=3)[S:41][C:34]=12

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 213259391-(Piperidin-1-yl)imidazolidin-2-oneHCID 594245073-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine

Product 1

HCID 58790362N-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-(piperidin-1-yl)imidazolidine-1-carboxamideYield 91.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triphosgene (107 mg, 0.36 mmol) was added to a solution of 1-(piperidin-1-yl)imidazolidin-2-one (278) (120 mg, 0.71 mmol) in THF (7.1 mL) and the mixture was refluxed 6 h the solution was cooled down. 3-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)aniline (12) (150.0 mg, 0.44 mmol) and DIPEA (0.186 mL, 1.07 mmol) were added and the mixture stirred 1 h at room temperature. The reaction mixture was filtered, the solution transferred to a flash chromatography column and eluted with 2% to 5% MeOH in DCM affording title compound 276 (176.4 mg, 0.33 mmol, 75% yield) as a creamy solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.57 (s, 1H), 8.4 (d, J=5.4 Hz, 1H), 7.86 (s, 1H), 7.79 (dd, J=2 Hz, J=12.9 Hz, 1H), 7.72 (s, 1H), 7.68 (s, 1H), 7.46 (t, J=8.9 Hz, 1H), 7.36 (m, 1H), 6.58 (d, 5.4 Hz, 1H), 3.76 (dd, J=7.7 Hz, J=8.2 Hz, 2H), 3.73 (s, 3H), 3.54 (dd, J=8.2 Hz, J=7.7 Hz, 2H), 2.9-2.87 (m, 4H), 1.59 (m, 4H), 1.35 (m, 2H). MS (m/z): (M+1) 536.2 (100%)

Workup

  1. temperaturethe mixture was refluxed 6 h the solution
  2. temperaturewas cooled down
  3. filtrationThe reaction mixture was filtered

Sources & evidence

ORD record
ord-c9ca46578f5b4aa0bc085466bdfec3e9
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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