Pyridine → HCID 86268213, compound

HRID 2278999Notes

Reaction equation

HRID 2278999 reaction equation
[C:1](Cl)(Cl)=[O:2].N1C=CC=CC=1.[CH3:11][CH:12]1[N:16]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:15](=[O:23])[NH:14][CH2:13]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>[CH3:11][CH:12]1[CH2:13][N:14]([C:1]([NH:43][C:40]2[CH:39]=[CH:38][C:37]([O:36][C:34]3[CH:33]=[CH:32][N:31]=[C:30]([C:28]4[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=4)[CH:35]=3)=[CH:42][N:41]=2)=[O:2])[C:15](=[O:23])[N:16]1[CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 6371PhosgeneHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineHCID 117653594HCID 117653594, compound

Product 1

HCID 86268213HCID 86268213, compoundYield 9%

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 5-methyl-1-(tetrahydro-2H-pyran-4-yl)imidazolidin-2-one (0.103 g, 0.561 mmol) in DCM (5 mL), stirred at RT for 1 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 overnight. The solids were removed via filtration, washed with DCM and the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 4-methyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (16 mg, 9%). 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.23 (d, J=2.9 Hz, 1 H), 8.06 (d, J=9.0 Hz, 1 H), 7.95 (s, 1 H), 7.71 (dd, J=9.0, 2.9 Hz, 1 H), 7.22 (d, J=2.4 Hz, 1 H), 6.68 (dd, J=5.7, 2.4 Hz, 1 H), 3.90 (m, 4H), 3.87 (m, 1 H), 3.84 (s, 3 H), 3.66 (m, 1 H), 3.39 (m, 1 H), 3.34 (m, 1 H), 2.05 (m, 1 H), 1.90 (m, 1 H), 1.70 (m, 1 H), 1.68 (m, 1 H), 1.28 (d, J=5.4 Hz, 3H); MS (ESI) m/z: 478.2 (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 overnight
  6. customThe solids were removed via filtration
  7. washwashed with DCM
  8. concentrationthe filtrate concentrated to dryness
  9. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-9290e17c0a0f48678c2944be54115b21
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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