Pyridine → HCID 86268612, compound

HRID 2279005Notes

Reaction equation

HRID 2279005 reaction equation
[C:1](Cl)(Cl)=[O:2].[O:5]=[C:6]1[NH:10][CH2:9][CH2:8][N:7]1[CH2:11][C:12]#[N:13].N1C=CC=CC=1.[CH3:20][N:21]1[CH:25]=[C:24]([C:26]2[CH:31]=[C:30]([O:32][C:33]3[CH:34]=[CH:35][C:36]([NH2:39])=[N:37][CH:38]=3)[CH:29]=[CH:28][N:27]=2)[CH:23]=[N:22]1>C(Cl)Cl>[C:12]([CH2:11][N:7]1[CH2:8][CH2:9][N:10]([C:6]([NH:39][C:36]2[CH:35]=[CH:34][C:33]([O:32][C:30]3[CH:29]=[CH:28][N:27]=[C:26]([C:24]4[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=4)[CH:31]=3)=[CH:38][N:37]=2)=[O:5])[C:1]1=[O:2])#[N:13]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 6371PhosgeneHCID 20669979HCID 20669979, compoundHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

Product 1

HCID 86268612HCID 86268612, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A 0° C. solution of phosgene (15% in toluene, 1.37 mL, 1.948 mmol) in DCM (5 mL) was treated drop-wise with a solution of 2-(2-oxoimidazolidin-1-yl)acetonitrile (0.065 g, 0.519 mmol) and pyridine (0.2 mL, 2.473 mmol) in DCM (5 mL), warmed to RT, stirred 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 (0.069 g, 0.260 mmol) and pyridine (0.2 mL) in DCM (5 mL), warmed to RT and stirred for 3 h. The mixture was treated with satd. NaHCO3, extracted with DCM (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc) to afford 3-(cyanomethyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (25 mg, 22%). 1H NMR (400 MHz, DMSO-d6): δ 10.69 (s, 1 H), 8.37 (d, J=5.7 Hz, 1 H), 8.25-8.24 (m, 2 H), 8.07 (d, J=9.0 Hz, 1 H), 7.96 (d, J=0.7 Hz, 1 H), 7.74 (dd, J=9.0, 2.9 Hz, 1 H), 7.23 (d, J=2.4 Hz, 1 H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 4.47 (s, 2 H), 3.93-3.84 (m, 5 H), 3.54 (t, J=8.2 Hz, 2H); MS (ESI) m/z: 419.2 (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 3 h
  6. additionThe mixture was treated with satd
  7. extractionNaHCO3, extracted with DCM (3×)
  8. dry with materialthe combined organics were dried over Na2SO4
  9. concentrationconcentrated to dryness
  10. custompurified via silica gel chromatography (MeOH/EtOAc)

Sources & evidence

ORD record
ord-03ab888713cc45e7abab6f6b05cfeb42
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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