Pyridine → HCID 86269849, compound

HRID 2279017Notes

Reaction equation

HRID 2279017 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH3:5][N:6]1[CH2:10][CH2:9][NH:8][C:7]1=[O:11].N1C=CC=CC=1.[CH3:18][C:19]1[C:24]([O:25][C:26]2[CH:31]=[CH:30][N:29]=[C:28]([C:32]3[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=3)[CH:27]=2)=[CH:23][N:22]=[C:21]([NH2:38])[CH:20]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:5][N:6]1[CH2:10][CH2:9][N:8]([C:7]([NH:38][C:21]2[CH:20]=[C:19]([CH3:18])[C:24]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([C:32]4[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=4)[CH:27]=3)=[CH:23][N:22]=2)=[O:11])[C:1]1=[O:2]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 5676001-Methylimidazolidin-2-oneHCID 686640964-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine

Product 1

HCID 86269849HCID 86269849, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A 0° C. solution of phosgene (15% in toluene, 2.82 mL, 4.00 mmol) in DCM (3 mL) was treated drop-wise with a solution of 1-methyl-2-imidazolidinone (0.107 g, 1.066 mmol) and pyridine (0.2 mL, 2.473 mmol) in DCM (3 mL), warmed to RT, stirred for 0.5 h, then concentrated to dryness. The residue was dissolved in DCM (3 mL), cooled to 0° C., treated with a solution of 4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.15 g, 0.533 mmol) and DIEA (0.2 mL, 1.145 mmol) in DCM (3 mL), warmed to RT and stirred for 3 h. The mixture was treated with satd. NaHCO3, extracted with DCM (4×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN and the resulting solid was collected via filtration to afford 3-methyl-N-(4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (116 mg, 52%). 1H NMR (400 MHz, DMSO-d6): δ 10.90 (s, 1 H), 8.34 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.10 (s, 1 H), 8.01 (s, 1 H), 7.95 (s, 1 H), 7.16 (d, J=2.4 Hz, 1 H), 6.59 (dd, J=5.7, 2.5 Hz, 1 H), 3.84 (s, 3 H), 3.79-3.78 (m, 2 H), 3.45 (t, J=8.2 Hz, 2 H), 2.80 (s, 3 H), 2.14 (s, 3H); MS (ESI) m/z: 408.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (3 mL)
  3. temperaturecooled to 0° C.
  4. temperaturewarmed to RT
  5. stirringstirred for 3 h
  6. additionThe mixture was treated with satd
  7. extractionNaHCO3, extracted with DCM (4×)
  8. dry with materialthe combined organics were dried over Na2SO4
  9. concentrationconcentrated to dryness
  10. additionThe material was treated with MeCN
  11. filtrationthe resulting solid was collected via filtration

Sources & evidence

ORD record
ord-c6df30d42b214058884cb71bbb63bed8
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

Loading…