N-(4-(4-methyl-2-propyl-1H-imidazol-1-yl)thiazol-5-yl)acetamide → 5,6-Dimethyl-8-propyl-3-thia-1,4,7,8a-tetraaza-as-indacene

HRID 1051419Notes

Reaction equation

HRID 1051419 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([CH2:16][CH2:17][CH3:18])[N:5]([C:7]2[N:8]=[CH:9][S:10][C:11]=2[NH:12][C:13](=O)[CH3:14])[CH:6]=1.[P].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>O=P(Cl)(Cl)Cl>[CH3:14][C:13]1[C:6]2[N:5]([C:4]([CH2:16][CH2:17][CH3:18])=[N:3][C:2]=2[CH3:1])[C:7]2[N:8]=[CH:9][S:10][C:11]=2[N:12]=1

Participants

4

Reactant 2

HCID 86715554N-(4-(4-methyl-2-propyl-1H-imidazol-1-yl)thiazol-5-yl)acetamideHCID 178526998HCID 178526998, compound

Product 1

HCID 734258565,6-Dimethyl-8-propyl-3-thia-1,4,7,8a-tetraaza-as-indaceneYield 53.7%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of N-(4-(4-methyl-2-propyl-1H-imidazol-1-yl)thiazol-5-yl)acetamide from example 1.7 (10 mg, 0.038 mmol) in POCl3 (3 mL) was quickly added phosphorus P2O5 (10.74 mg, 0.076 mmol). The reaction mixture was refluxed at 110° C. for 4 h. POCl3 was evaporated and the residue was carefully quenched with ice-water. The mixture was neutralized with saturated Na2CO3 solution and extracted with ethyl acetate (3×30 mL). The combined organic layer was washed with brine and concentrated to give brown liquid and then purified by pre-HPLC to give the title compound (5 mg, 0.02 mmol, 53.7%) as a white solid.

Workup

  1. customPOCl3 was evaporated
  2. customthe residue was carefully quenched with ice-water
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. washThe combined organic layer was washed with brine
  5. concentrationconcentrated
  6. customto give brown liquid
  7. custompurified by pre-HPLC

Sources & evidence

ORD record
ord-a99ca0efae3e4951a8545b5c048d7ae0
Source dataset
uspto-grants-2016_07
Patent number
US09388180B2

Reaction notes

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