Pyridine → HCID 86270403, compound

HRID 2278984Notes

Reaction equation

HRID 2278984 reaction equation
[C:1](Cl)(Cl)=[O:2].[O:5]1[CH2:9][CH2:8][C@H:7]([N:10]2[CH2:14][CH2:13][NH:12][C:11]2=[O:15])[CH2:6]1.N1C=CC=CC=1.[CH3:22][N:23]1[CH:27]=[C:26]([C:28]2[CH:33]=[C:32]([O:34][C:35]3[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=3)[CH:31]=[CH:30][N:29]=2)[CH:25]=[N:24]1>C(Cl)Cl.O>[CH3:22][N:23]1[CH:27]=[C:26]([C:28]2[CH:33]=[C:32]([O:34][C:35]3[CH:36]=[CH:37][C:38]([NH:41][C:11]([N:12]4[CH2:13][CH2:14][N:10]([C@H:7]5[CH2:8][CH2:9][O:5][CH2:6]5)[C:1]4=[O:2])=[O:15])=[N:39][CH:40]=3)[CH:31]=[CH:30][N:29]=2)[CH:25]=[N:24]1

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 6371PhosgeneHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineHCID 90427717HCID 90427717, compound

Product 1

HCID 86270403HCID 86270403, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of phosgene (20% in toluene, 0.092 mL, 0.174 mmol) in DCM (2 mL) was treated slowly with a solution of Example B6 (26 mg, 0.166 mmol) and pyridine (0.027 mL, 0.331 mmol) in DCM (2 mL), stirred at 0° C. for 0.5 h, then concentrated to dryness. The residue was dissolved in DCM (2 mL), treated with pyridine (0.0400 mL, 0.495 mmol), cooled to 0° C., treated slowly with a solution of Example A2 (36 mg, 0.165 mmol) in DCM (2 mL), warmed to RT and stirred for 1.5 h. The mixture was diluted with water, extracted with DCM and the organic layer was washed with water, then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford (S)—N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydrofuran-3-yl)imidazolidine-1-carboxamide (33 mg, 45%). 1H NMR (400 MHz, DMSO-d6): δ 10.95 (s, 1 H), 8.38 (d, J=5.8 Hz, 1 H), 8.27 (s, 1 H), 8.23 (d, J=2.9 Hz, 1 H), 8.07 (d, J=9.0 Hz, 1 H), 7.97 (s, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.25 (s, 1 H), 6.71 (d, J=5.5 Hz, 1 H), 4.57-4.49 (m, 1 H), 3.91-3.86 (m, 1 H), 3.84 (s, 3 H), 3.83-3.76 (m, 3 H), 3.70-3.57 (m, 2 H), 3.51-3.43 (m, 2 H), 2.19-2.09 (m, 1 H), 2.02-1.91 (m, 1 H); MS (ESI) m/z: 450.1 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. temperaturecooled to 0° C.
  4. temperaturewarmed to RT
  5. stirringstirred for 1.5 h
  6. extractionextracted with DCM
  7. washthe organic layer was washed with water
  8. dry with materialbrine, dried over Na2SO4
  9. concentrationconcentrated to dryness
  10. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-be8f4a1d4af9425a91fd791563235a08
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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