Phosphorus oxide (P4O10) → 5,6-Dimethyl-8-propyl-1-thia-3,4,7,8a-tetraaza-as-indacene

HRID 1051424Notes

Reaction equation

HRID 1051424 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([CH2:16][CH2:17][CH3:18])[N:5]([C:7]2[S:11][CH:10]=[N:9][C:8]=2[NH:12][C:13](=O)[CH3:14])[CH:6]=1.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[S:11][CH:10]=[N:9][C:8]=2[N:12]=1

Participants

4

Reactant 3

HCID 14812Phosphorus oxide (P4O10)HCID 24813Phosphorus oxychlorideHCID 86715557N-(5-(4-methyl-2-propyl-1H-imidazol-1-yl)thiazol-4-yl)acetamide

Product 1

HCID 734259765,6-Dimethyl-8-propyl-1-thia-3,4,7,8a-tetraaza-as-indaceneYield 67.1%

Conditions

Temperature
110 °C

Procedure

N-(5-(4-methyl-2-propyl-1H-imidazol-1-yl)thiazol-4-yl)acetamide from example 2.5 (8 mg, 0.030 mmol) and phosphorus pentoxide (21.48 mg, 0.15 mmol) were added sequentially quickly to POCl3 (5 mL). The mixture was heated to 110° C. for 4 h, POCl3 was evaporated and the residue was quenched with ice-water. The mixture was neutralized with saturated Na2CO3 solution and extracted with EA (3×20 mL). The combined organic layer was washed with brine and concentrated to give brown liquid. It was purified by pre-HPLC to give the title compound (5.0 mg, 0.02 mmol, 67.1%) as a white solid.

Workup

  1. customPOCl3 was evaporated
  2. customthe residue was quenched with ice-water
  3. extractionextracted with EA (3×20 mL)
  4. washThe combined organic layer was washed with brine
  5. concentrationconcentrated
  6. customto give brown liquid
  7. customIt was purified by pre-HPLC

Sources & evidence

ORD record
ord-af0552827f0b46b49ec0bc4c40cae036
Source dataset
uspto-grants-2016_07
Patent number
US09388180B2

Reaction notes

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