Chlorotrimethylsilane → 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,4]triazol-4-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester

HRID 2280285Notes

Reaction equation

HRID 2280285 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[N:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][C:20]=2[CH3:28])[C:9]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)[CH3:2].[CH:30]([NH:32][NH:33][CH:34]=O)=O.Cl[Si](C)(C)C.C(N(CC)CC)C>N1C=CC=CC=1.O>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[N:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][C:20]=2[CH3:28])[C:9]([C:12]2[CH:13]=[CH:14][C:15]([N:18]3[CH:34]=[N:33][N:32]=[CH:30]3)=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)[CH3:2]

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 123421,2-HydrazinedicarboxaldehydeHCID 583056233-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]propanoic acid ethyl ester

Product 1

HCID 583056703-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,4]triazol-4-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

Under a nitrogen atmosphere, 3-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (11A, synthesis described in Scheme 4 where R1=4-carbamoyl-2-methylphenyl) (102 mg, 0.26 mmol) was dissolved in 4 mL pyridine. 1,2-diformylhydrazine (69 mg, 0.78 mmol) was added. Chlorotrimethylsilane (0.5 mL, 3.9 mmol) was added dropwise. Triethylamine (0.25 mL, 1.82 mmol) was added dropwise. The reaction was heated to 100° C. for 24 hrs. After cooling, the reaction was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by preparative tlc plate (1500 microns, 10% IPA/CH2Cl2). The desired band (rf=0.3) was isolated and dried under high vacuum to yield 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,4]triazol-4-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (11B) (95 mg, 82%, light tan powder).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by preparative tlc plate (1500 microns, 10% IPA/CH2Cl2)
  8. customThe desired band (rf=0.3) was isolated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-3b272e42bfc74672b3f453881946b492
Source dataset
uspto-grants-2015_09
Patent number
US09138427B2

Reaction notes

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