Phosgene → 4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid (3-methyl-pyridin-2-yl)-amide

HRID 557767Notes

Reaction equation

HRID 557767 reaction equation
[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[C:16](Cl)(Cl)=[O:17].C1COCC1.Cl.[N:26]1([C:32]2[CH:37]=[CH:36][C:35]([NH:38][C:39]([C:41]3[N:42]=[C:43]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[O:44][C:45]=3[C:46]([F:49])([F:48])[F:47])=[O:40])=[CH:34][CH:33]=2)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>C(Cl)Cl.CN1CCCC1=O.C(OCC)(=O)C>[CH3:8][C:7]1[C:2]([NH:1][C:16]([N:29]2[CH2:30][CH2:31][N:26]([C:32]3[CH:37]=[CH:36][C:35]([NH:38][C:39]([C:41]4[N:42]=[C:43]([C:50]5[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=5)[O:44][C:45]=4[C:46]([F:47])([F:49])[F:48])=[O:40])=[CH:34][CH:33]=3)[CH2:27][CH2:28]2)=[O:17])=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 5

HCID 6371PhosgeneHCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 153472-Amino-3-methylpyridineHCID 667383362-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-piperazin-1-yl-phenyl)-amide hydrochloride

Product 1

HCID 576520304-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid (3-methyl-pyridin-2-yl)-amideYield 16%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 2-amino-3-picoline (26 μL, 0.204 mmol) and triethylamine (63 □L, 0.448 mmol) in 5 mL methylene chloride at −40° C. was slowly added a 20% solution of phosgene in THF (118 μL, 0.224 mmol). The reaction mixture was stirred at −40° C. for 1 hr and then a solution of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-piperazin-1-yl-phenyl)-amide hydrochloride (100 mg, 0.204 mmol) and triethylamine (57 μl, 0.408 mmol) in 8 ml of 1-methyl-2-pyrrolidinone was slowly added and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic layer was dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography (eluting with ethyl acetate/hexane) to yield 4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid (3-methyl-pyridin-2-yl)-amide (18 mg, 16%). ES-MS calcd for C28H25F3N6O3 (m/e) 550.6, obsd 551.1 (M+H).

Workup

  1. stirringstirred at room temperature overnight
  2. washwashed with saturated sodium bicarbonate solution and water
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by flash chromatography (eluting with ethyl acetate/hexane)

Sources & evidence

ORD record
ord-181478ef37dd4302948c3fd84f72e8e5
Source dataset
uspto-grants-2011_11
Patent number
US08058299B2

Reaction notes

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