4-Chlorobenzaldehyde → 4-acetyl-5-(4-chlorophenyl)-1-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-hydroxy-1H-pyrrol-2(5H)-one

HRID 873952Notes

Reaction equation

HRID 873952 reaction equation
[CH3:1][C:2]1[N:6]2[CH:7]=[C:8]([NH2:12])[CH:9]=[C:10]([CH3:11])[C:5]2=[N:4][N:3]=1.[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1.[O:22]=[C:23]([CH2:29][C:30](=[O:32])[CH3:31])[C:24](OCC)=[O:25]>C(O)(=O)C>[C:30]([C:29]1[CH:18]([C:17]2[CH:20]=[CH:21][C:14]([Cl:13])=[CH:15][CH:16]=2)[N:12]([C:8]2[CH:9]=[C:10]([CH3:11])[C:5]3[N:6]([C:2]([CH3:1])=[N:3][N:4]=3)[CH:7]=2)[C:24](=[O:25])[C:23]=1[OH:22])(=[O:32])[CH3:31]

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 69208Ethyl 2,4-dioxovalerateHCID 753574493,8-Dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-amine

Product 1

HCID 1177026714-acetyl-5-(4-chlorophenyl)-1-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-hydroxy-1H-pyrrol-2(5H)-oneYield 79%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-amine (Step 67.4) (2 g, 12.33 mmol), 4-chlorobenzaldehyde (1.576 g, 11.21 mmol) and ethyl 2,4-dioxopentanoate (1.773 g, 11.21 mmol) in acetic acid (10 mL) was stirred for 2 hr at 100° C. The reaction mixture was concentrated, diluted with CH2Cl2/1N NaOH and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, evaporated and discarded as they contained no desired product. The aqueous was acidified to pH 3 with 6N HCl and extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4 and concentrated to afford the title compound (3.88 g, 8.80 mmol, 79% yield) as a beige foam. tR: 0.70 min (LC-MS 2); ESI-MS: 397 [M+H]+ (LC-MS 2); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (s, 3H) 2.44 (s, 3H) 2.63 (s, 3H) 6.14 (s, 1H) 7.27 (d, J=8.44 Hz, 2H) 7.33-7.40 (m, 3H) 8.53 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with CH2Cl2/1N NaOH
  3. extractionextracted with CH2Cl2
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. customevaporated
  6. extractionextracted with CH2Cl2
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9d6c9abe45054eff8b53b91cf599c4fd
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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