Pyridine → N-(2,4-di-tert-butyl-5-hydroxyphenyl)-7-ethyl-4-oxo-1,4-dihydropyrrolo[1,2-a]pyrimidine-3-carboxamide

HRID 2171307Notes

Reaction equation

HRID 2171307 reaction equation
[CH2:1]([C:3]1[CH:4]=[C:5]2[NH:10][CH:9]=[C:8]([C:11]([OH:13])=O)[C:7](=[O:14])[N:6]2[CH:15]=1)[CH3:2].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.N1C=CC=CC=1.[NH2:40][C:41]1[C:42]([C:52]([CH3:55])([CH3:54])[CH3:53])=[CH:43][C:44]([C:48]([CH3:51])([CH3:50])[CH3:49])=[C:45]([OH:47])[CH:46]=1>CC1CCCO1>[C:52]([C:42]1[CH:43]=[C:44]([C:48]([CH3:51])([CH3:50])[CH3:49])[C:45]([OH:47])=[CH:46][C:41]=1[NH:40][C:11]([C:8]1[C:7](=[O:14])[N:6]2[CH:15]=[C:3]([CH2:1][CH3:2])[CH:4]=[C:5]2[NH:10][CH:9]=1)=[O:13])([CH3:55])([CH3:53])[CH3:54]

Participants

6

Reactant 4

HCID 1049PyridineHCID 111923Propylphosphonic anhydrideHCID 441762265-Amino-2,4-di-tert-butylphenolHCID 66859447HCID 66859447, compound

Product 1

HCID 42642292N-(2,4-di-tert-butyl-5-hydroxyphenyl)-7-ethyl-4-oxo-1,4-dihydropyrrolo[1,2-a]pyrimidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 7-ethyl-4-oxo-1,4-dihydropyrrolo[1,2-a]pyrimidine-3-carboxylic acid (32.3 mg, 0.1566 mmol) in 2-methyltetrahydrofuran (400 μL) was added 1-Propanephosphonic acid cyclic anhydride (249.1 mg, 233.0 μL, 0.3915 mmol) followed by the addition of pyridine (24.77 mg, 25.33 μL, 0.3132 mmol). The reaction was sealed and heated at 45° C. for 30 minutes upon which 5-amino-2,4-di-tert-butylphenol (41.59 mg, 0.1879 mmol) was added and the reaction was heated at 45° C. for 16 h. The solvent was removed in vacuo and the residue was purified by reverse phase HPLC (40-100% acetonitrile with 0.035% TFA in water with 0.05% TFA) to give N-(2,4-di-tert-butyl-5-hydroxyphenyl)-7-ethyl-4-oxo-1,4-dihydropyrrolo[1,2-a]pyrimidine-3-carboxamide. LC/MS (10-99% CH3CN/0.05% TFA in H2O/0.05% TFA gradient over 3 min): M+H m/z 410.5, retention time 2.24 minutes. 1H NMR (400.0 MHz, DMSO) δ 13.07 (d, J=6.6 Hz, 1H), 10.72 (s, 1H), 9.20 (s, 1H), 8.55 (d, J=6.8 Hz, 1H), 7.32 (s, 1H), 7.16 (s, 1H), 7.11 (s, 1H), 6.11 (d, J=1.7 Hz, 1H), 2.59 (q, J=7.5 Hz, 2H), 1.36 (s, 18H) and 1.22 (t, J=7.5 Hz, 3H).

Workup

  1. customThe reaction was sealed
  2. additionwas added
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by reverse phase HPLC (40-100% acetonitrile with 0.035% TFA in water with 0.05% TFA)

Sources & evidence

ORD record
ord-a88a086194c245729e251093ea2b18ac
Source dataset
uspto-grants-2015_06
Patent number
US09051324B2

Reaction notes

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