Diisopropylethylamine → N-(4-(2-(1-ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamide

HRID 418663Notes

Reaction equation

HRID 418663 reaction equation
[C:1]1([N:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:25]([N:27]1[CH:31]=[C:30]([C:32]2[S:40][C:39]3[C:34](=[N:35][CH:36]=[CH:37][C:38]=3[O:41][C:42]3[CH:47]=[CH:46][C:45]([NH2:48])=[CH:44][C:43]=3[F:49])[CH:33]=2)[N:29]=[CH:28]1)[CH3:26].CCN(C(C)C)C(C)C>C1COCC1>[CH2:25]([N:27]1[CH:31]=[C:30]([C:32]2[S:40][C:39]3[C:34](=[N:35][CH:36]=[CH:37][C:38]=3[O:41][C:42]3[CH:47]=[CH:46][C:45]([NH:48][C:14]([N:9]4[CH2:10][CH2:11][N:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[C:8]4=[O:12])=[O:16])=[CH:44][C:43]=3[F:49])[CH:33]=2)[N:29]=[CH:28]1)[CH3:26]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 2552731-Phenylimidazolidin-2-oneHCID 594244554-(2-(1-Ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorobenzenamine

Product 1

HCID 16040363N-(4-(2-(1-ethyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamideYield 44.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-phenylimidazolidin-2-one (211) (100 mg, 0.62 mmol) [P. Mayer, P. Brunel, C. Chaplain, C. Piedecoq, F. Calmel, P. Schambel, P. Chopin, T. Wurch, P. J. Pauwels, M. Marien, J.-L. Vidaluc, T. Imbert J. Med. Chem. 2000, 43, 3653-3664; W. Su, Y. Zhang J. Chem. Res. Synop. 2000, 9, 440-441] in THF (6 mL) was added triphosgene (189 mg, 0.62 mmol) and the solution was stirred for 3 hrs at 60° C. The reaction mixture was cooled to RT before the addition of aniline 15 (229 mg, 0.65 mmol) and DIPEA (648 μL, 3.72 mmol) and stirring was continued for an hour. The reaction mixture was concentrated and partitioned between EtOAc and water. A precipitate was formed which was collected by filtration. The organic layer was separated, dried and concentrated. The residue was combined with the collected precipitate, dry loaded to a column and eluted with EtOAc/MeOH (9:1), to produce title compound 210 (150 mg, 43% yield) as an off-white solid. 1H NMR (DMSO-d6) δ (ppm): 10.57 (s, 1H), 8.42 (d, J=5.5 Hz, 1H), 7.95 (d, J=1.1 Hz, 1H), 7.83 (dd, J=2.5 and 13.3 Hz, 2H), 7.77 (d, J=1.2 Hz, 1H), 7.66 (s, 1H), 7.61 (dd, J=1.0 and 8.8 Hz, 1H), 7.49-7.41 (m, 4H), 7.16 (t, J=7.2 Hz, 1H), 6.57 (d, J=5.5 Hz, 1H), 4.03 (q, 2H), 4.04-3.92 (m, 4H), 1.38 (t, 3H). MS (m/z): 543.0 (M+H).

Workup

  1. stirringstirring
  2. waitwas continued for an hour
  3. concentrationThe reaction mixture was concentrated
  4. custompartitioned between EtOAc and water
  5. customA precipitate was formed which
  6. filtrationwas collected by filtration
  7. customThe organic layer was separated
  8. customdried
  9. concentrationconcentrated
  10. customdry loaded to a column
  11. washeluted with EtOAc/MeOH (9:1)

Sources & evidence

ORD record
ord-ea7bb75bef5448a09727bf4cbbe1f853
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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