Pyridine → HCID 86267373, compound

HRID 2278994Notes

Reaction equation

HRID 2278994 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH3:5][O:6][C:7]1([CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][NH:14][C:13]2=[O:17])[CH2:9][CH2:8]1.N1C=CC=CC=1.[CH3:24][N:25]1[CH:29]=[C:28]([C:30]2[CH:35]=[C:34]([O:36][C:37]3[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=3)[CH:33]=[CH:32][N:31]=2)[CH:27]=[N:26]1>C(Cl)Cl.O>[CH3:5][O:6][C:7]1([CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][N:14]([C:13]([NH:43][C:40]3[CH:39]=[CH:38][C:37]([O:36][C:34]4[CH:33]=[CH:32][N:31]=[C:30]([C:28]5[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=5)[CH:35]=4)=[CH:42][N:41]=3)=[O:17])[C:1]2=[O:2])[CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6371PhosgeneHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineHCID 90426481HCID 90426481, compound

Product 1

HCID 86267373HCID 86267373, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A 0° C. solution of phosgene (20% in toluene, 0.711 mL, 0.980 mmol) in DCM (6 mL) was treated slowly drop-wise with a solution of Example B9 (0.129 g, 0.700 mmol) and pyridine (0.113 mL, 1.400 mmol) in DCM (2 mL), warmed to RT, stirred for 0.5 h, then concentrated to dryness. The residue was dissolved in DCM (2 mL), added to a 0° C. solution of Example A2 (0.058 g, 0.218 mmol) and TEA (0.091 mL, 0.654 mmol) in DCM (1 mL), warmed to RT and stirred for 0.5 h. The mixture was treated with water, stirred for 15 min and the layers separated. The organic layer was washed with additional water (2×), dried over MgSO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 3-(2-(1-methoxycyclopropyl)ethyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (25 mg, 24%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.99 (s, 1 H), 8.37 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.22 (d, J=2.9 Hz, 1 H), 8.07 (d, J=9.0 Hz, 1 H), 7.96 (d, J=0.7 Hz, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.22 (d, J=2.4 Hz, 1 H), 6.69 (dd, J=5.7, 2.4 Hz, 1 H), 3.84 (s, 3 H), 3.80 (m, 2 H), 3.50 (m, 2 H), 3.34 (m, 2 H), 3.17 (s, 3 H), 1.77 (t, J=7.4 Hz, 2 H), 0.67 (m, 2 H), 0.42 (m, 2 H); MS (ESI) m/z: 478.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. temperaturewarmed to RT
  4. stirringstirred for 0.5 h
  5. stirringstirred for 15 min
  6. customthe layers separated
  7. washThe organic layer was washed with additional water (2×)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated to dryness
  10. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-584ecc6f28464e4f8e3e9529dd71158a
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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