Phenyl Isothiocyanate → (RS) 3-{5-[2-(2-Phenylamino-benzoxazol-6-yl)-acetylamino]-pyridin-2-yl}-butyric acid

HRID 49699

Reaction equation

HRID 49699 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([CH:18]([CH3:24])[CH2:19][C:20]([O:22]C)=[O:21])=[N:16][CH:17]=2)=[O:10])=[CH:4][C:3]=1[OH:25].[C:26]1([N:32]=[C:33]=S)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(O)C>[C:26]1([NH:32][C:33]2[O:25][C:3]3[CH:4]=[C:5]([CH2:8][C:9]([NH:11][C:12]4[CH:13]=[CH:14][C:15]([CH:18]([CH3:24])[CH2:19][C:20]([OH:22])=[O:21])=[N:16][CH:17]=4)=[O:10])[CH:6]=[CH:7][C:2]=3[N:1]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 7673Phenyl IsothiocyanateHCID 17946638(RS) Methyl 3-{5-[2-(4-amino-3-hydroxy-phenyl)-acetylamino]-pyridin-2-yl}-butanoate

Product 1

HCID 9932413(RS) 3-{5-[2-(2-Phenylamino-benzoxazol-6-yl)-acetylamino]-pyridin-2-yl}-butyric acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of (RS) methyl 3-{5-[2-(4-amino-3-hydroxy-phenyl)-acetylamino]-pyridin-2-yl}-butyrate (41.2 mg, Reference Example 24) in ethanol (1 mL) was treated with a solution of phenyl isothiocyanate (16.23 mg) in ethanol (2 mL). The mixture allowed to stand at room temperature for 48 hours, then heated at 70° C. for 16 hours and then evaporated. The residue, (RS) methyl 3-{5-[2-(3-hydroxy-4-(3-phenylthioureido)-phenyl)-acetylamino]-pyridin-2-yl}-butyrate, was dissolved in dry dimethylformamide (1 mL) and the solution was treated with a solution of dicyclohexylcarbodiimide (74.2 mg) in dry dimethylformamide (2 mL). This mixture was heated at 70° C. for 12 hours and then evaporated. The residue was dissolved in methanol (2 mL) and the solution was treated with aqueous sodium hydroxide (600 μL, 1M). After shaking for 24 hours the mixture was filtered and the filtrate was acidified with aqueous acetic acid (1 mL, 1M). The precipitate was filtered and dissolved in dimethylformamide. This solution was evaporated and the residue was subjected to reversed phase HPLC on a Hypersil Elite C18 column (100 mm×21 mm) using 0.05% TFA in acetonitrile water to give the title compound. LC-MS: RT=2.36 minutes; MS (ES+): 431 (MH+).

Workup

  1. customevaporated
  2. dissolutionThe residue, (RS) methyl 3-{5-[2-(3-hydroxy-4-(3-phenylthioureido)-phenyl)-acetylamino]-pyridin-2-yl}-butyrate, was dissolved in dry dimethylformamide (1 mL)
  3. additionthe solution was treated with a solution of dicyclohexylcarbodiimide (74.2 mg) in dry dimethylformamide (2 mL)
  4. temperatureThis mixture was heated at 70° C. for 12 hours
  5. customevaporated
  6. dissolutionThe residue was dissolved in methanol (2 mL)
  7. additionthe solution was treated with aqueous sodium hydroxide (600 μL, 1M)
  8. filtrationwas filtered
  9. filtrationThe precipitate was filtered
  10. dissolutiondissolved in dimethylformamide
  11. customThis solution was evaporated

Sources & evidence

ORD record
ord-f8d5ec0155544f74bdc4baec67ad2b40
Source dataset
uspto-grants-2004_03
Patent number
US06706738B2

Linked notes

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