Pyridine → HCID 86268217, compound

HRID 2279000Notes

Reaction equation

HRID 2279000 reaction equation
[C:1](Cl)(Cl)=[O:2].N1C=CC=CC=1.[CH3:11][N:12]1[CH2:16][CH2:15][NH:14][C:13]1=[O:17].[CH3:18][N:19]1[CH:23]=[C:22]([C:24]2[CH:29]=[C:28]([O:30][C:31]3[CH:32]=[CH:33][C:34]([NH2:37])=[N:35][CH:36]=3)[CH:27]=[CH:26][N:25]=2)[CH:21]=[N:20]1>C(Cl)Cl>[CH3:11][N:12]1[CH2:16][CH2:15][N:14]([C:13]([NH:37][C:34]2[CH:33]=[CH:32][C:31]([O:30][C:28]3[CH:27]=[CH:26][N:25]=[C:24]([C:22]4[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=4)[CH:29]=3)=[CH:36][N:35]=2)=[O:17])[C:1]1=[O:2]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 6371PhosgeneHCID 5676001-Methylimidazolidin-2-oneHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

Product 1

HCID 86268217HCID 86268217, compoundYield 54.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A 0° C. solution of phosgene (15% in toluene, 2 mL, 2.84 mmol) in DCM (5 mL) was treated drop-wise with a solution of pyridine (0.1 mL, 1.236 mmol) and 1-methylimidazolidin-2-one (0.056 g, 0.561 mmol) in DCM (5 mL), stirred at RT for 2 h, then concentrated to dryness. The residue was dissolved in DCM (5 mL), cooled to 0° C., treated with a solution of Example A2 (0.10 g, 0.374 mmol) and pyridine (0.1 mL) in DCM (5 mL), warmed to RT and stirred for 4 h. The solids were removed via filtration, washed with DCM and the filtrate concentrated to dryness. The residue was treated with EtOAc/DCM/MeCN, allowed to stand overnight and the resulting solid collected via filtration to afford 3-methyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (80 mg, 52%). 1H NMR (400 MHz, DMSO-d6): δ 11.04 (s, 1 H), 8.66 (s, 1 H), 8.52 (d, J=6.7 Hz, 1 H), 8.35 (s, 1 H), 8.32 (m, 1 H), 8.12 (d, J=9.1 Hz, 1 H), 7.83 (dd, J=9.1, 2.9 Hz, 1 H), 7.64 (s, 1 H), 7.13 (m, 1 H), 3.90 (s, 3 H), 3.80 (m, 2 H), 3.45 (m, 2 H), 2.80 (s, 3H); MS (ESI) m/z: 394.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. temperaturecooled to 0° C.
  4. temperaturewarmed to RT
  5. stirringstirred for 4 h
  6. customThe solids were removed via filtration
  7. washwashed with DCM
  8. concentrationthe filtrate concentrated to dryness
  9. additionThe residue was treated with EtOAc/DCM/MeCN
  10. waitto stand overnight
  11. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-36410719c6a346cab641d44a2ca47ad1
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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