Phosgene → HCID 10218444, compound

HRID 1824447Notes

Reaction equation

HRID 1824447 reaction equation
[NH2:1][C:2]1[N:3]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:4]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[CH:6]=1.C([O-])(O)=O.[Na+].C(Cl)(Cl)=O.[N-]=C=O.C(C1C=C(N[C:41]([NH:43][C:44]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]([O:54][C:55]3[CH:60]=[CH:59][N:58]=[C:57]([NH:61][CH2:62][CH:63]4[CH2:65][CH2:64]4)[N:56]=3)=[CH:46][CH:45]=2)=[O:42])N(C)N=1)(C)(C)C>C(Cl)Cl.C1(C)C=CC=CC=1.C1COCC1>[C:7]([C:5]1[CH:6]=[C:2]([NH:1][C:41]([NH:43][C:44]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]([O:54][C:55]3[CH:60]=[CH:59][N:58]=[C:57]([NH:61][CH2:62][CH:63]4[CH2:65][CH2:64]4)[N:56]=3)=[CH:46][CH:45]=2)=[O:42])[N:3]([C:11]2[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:4]=1)([CH3:10])([CH3:9])[CH3:8]

Participants

9

Reactant 5

HCID 6371PhosgeneHCID 105034IsocyanateHCID 516892Sodium BicarbonateHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 22147192HCID 22147192, compound

Product 1

HCID 10218444HCID 10218444, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-5-tert-butyl-2-(p-tolyl)-2H-pyrazole (2.39 g, 9.00 mmol, 1 equiv.) was dissolved in 35 mL methylene chloride and 35 mL saturated aqueous NaHCO3 was added. The biphasic mixture was stirred until all solids had completely dissolved and was then cooled to 0° C. The organic layer was then treated with phosgene in one portion via syringe while not stirring (15.8 mL of a 20% solution toluene, 31.5 mmol, 3.5 equiv.). The resulting mixture was stirred vigorously at 0° C. for 1 h. The organic layer was separated, dried (Na2SO4) and filtered. The methylene chloride was removed in vacuo and the resulting isocyanate in toluene was treated with a solution of aminonaphthyl-chloropyrimidyl ether intermediate (see Example 4) (2.45 g, 9.0 mmol, 1.0 equiv.) in 40 mL anhydrous THF. The mixture was stirred at room temperature for 3.5 h, then the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel using 0–10% MeOH in methylene chloride eluent mixtures, followed by recrystallization from ether, providing 1.90 g (40%) of the urea intermediate.

Workup

  1. dissolutionhad completely dissolved
  2. stirringThe resulting mixture was stirred vigorously at 0° C. for 1 h
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe methylene chloride was removed in vacuo
  7. stirringThe mixture was stirred at room temperature for 3.5 h
  8. customthe solvent was removed in vacuo
  9. customThe residue was purified by column chromatography on silica gel using 0–10% MeOH in methylene chloride eluent mixtures
  10. customfollowed by recrystallization from ether

Sources & evidence

ORD record
ord-8af70fdf728d4e61b923bd1cea7bdff6
Source dataset
uspto-grants-2006_05
Patent number
US07041669B2

Reaction notes

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