HCID 16051415, compound → HCID 16051416, compound

HRID 1363324Notes

Reaction equation

HRID 1363324 reaction equation
[NH2:1][C:2]1[N:6]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)=[O:8])[N:5]=[C:4]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23]CC3C=CC=CC=3)=[CH:19][CH:18]=2)[N:3]=1>C1CCCCC=1.C1COCC1.[Pd]>[NH2:1][C:2]1[N:6]([C:7]([C:9]2[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=2)=[O:8])[N:5]=[C:4]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=2)[N:3]=1

Participants

5

Reactant 1

HCID 16051415HCID 16051415, compound

Product 1

HCID 16051416HCID 16051416, compoundYield 35.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8079CyclohexeneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-amino-3-[4-(benzyloxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole (Ia-3) (3.95 g, 9.89 mmol) and 10% Pd/C (0.80 g) in cyclohexene (64 mL) and THF (128 mL) was stirred and heated at 70° C. After 2 d, additional 10% Pd/C (0.80 9) was added and heating and stirring at 70° C. was continued for an additional 3 d. After cooling to ambient temperature, the mixture was filtered through diatomaceous earth and concentrated to give a yellow-brown residue. Purification by flash chromatography (95:5 methylene chloride/methanol) followed by trituration with methylene chloride afforded 5-amino-3-[4-(hydroxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole (Ia-4) (1.08 g, 35%) as a pale yellow solid: Rf 0.36 (95:5 methylene chloride/methanol); mp 221-223° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.88 (s, 1H), 8.13 (d, J=8.2 Hz, 2H), 7.74 (br s, 2H), 7.38-7.32 (m, 4H), 6.64 (d, J=8.8 Hz, 2H), 2.42 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 166.1, 158.4, 157.3, 151.0, 142.9, 132.9, 130.6, 129.8, 128.4, 118.1, 115.1, 21.1; IR (ATR) 1697 cm−1; ESI MS m/z 310 [C16H15N5O2+H]+; HPLC (Method A) >99% (AUC), tR=11.22 min. Anal. Calcd for C16H15N5O2 0.5H2O: C, 60.47; H, 4.92; N, 22.04. Found: C, 60.27; H, 4.70; N, 21.51.

Workup

  1. temperatureheating
  2. stirringstirring at 70° C.
  3. waitwas continued for an additional 3 d
  4. temperatureAfter cooling to ambient temperature
  5. filtrationthe mixture was filtered through diatomaceous earth
  6. concentrationconcentrated
  7. customto give a yellow-brown residue
  8. customPurification by flash chromatography (95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-6f885e6781b340728d32785b065319c9
Source dataset
uspto-grants-2011_02
Patent number
US07884119B2

Reaction notes

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