Ammonium Hydroxide → 2-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-one

HRID 57713Notes

Reaction equation

HRID 57713 reaction equation
C[O:2][C:3]([C:5]1[N:6]([NH:10][C:11]([CH:13]2[CH:17]([CH3:18])[CH2:16][N:15]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:14]2)=O)[CH:7]=[N:8][CH:9]=1)=O.[OH-].[NH4+:27]>CO>[CH2:19]([N:15]1[CH2:16][CH:17]([CH3:18])[CH:13]([C:11]2[NH:27][C:3](=[O:2])[C:5]3=[CH:9][N:8]=[CH:7][N:6]3[N:10]=2)[CH2:14]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 14923Ammonium HydroxideHCID 897221853-[(1-Benzyl-4-methyl-pyrrolidine-3-carbonyl)-amino]-3H-imidazole-4-carboxylic acid methyl ester

Product 1

HCID 1365927602-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-oneYield 40.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
130 °C

Procedure

To a 300 mL sealed tube was added a mixture of compound 4 (4.7 g, 13.7 mmol), NH4OAc (11 g, 14.3 mmol) and ammonium hydroxide (50 mL) in MeOH (120 mL). The reaction mixture was stirred at 130° C. for 2 days. After cooling down, the reaction mixture was concentrated in vacuo. The residue was diluted with CH2Cl2 (100 mL) and washed with water (50 mL×2). The organic phase was separated and dried over Na2SO4. After filtering, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluted with DCM/MeOH=50:1 to 30:1) to afford compound 5 (1.8 g, 40.6% yield) as a white solid. LC-MS: m/z 310.17 [M+1]+. 1H NMR (400 MHz, CDCl3): δ 8.02 (s, 1H), 7.85 (s, 1H), 7.39˜7.28 (m, 5H), 3.82 (d, J=12.4 Hz, 1H), 3.58 (d, J=12.4 Hz, 1H), 3.41˜3.37 (m, 1H), 2.99 (d, J=6.4 Hz, 1H), 2.72˜2.70 (m, 1H), 2.54˜2.50 (m, 1H), 2.44˜2.40 (m, 1H), 1.95˜1.91 (m, 1H), 1.20 (d, J=6.4 Hz, 3H).

Workup

  1. customTo a 300 mL sealed tube
  2. additionwas added
  3. temperatureAfter cooling down
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. additionThe residue was diluted with CH2Cl2 (100 mL)
  6. washwashed with water (50 mL×2)
  7. customThe organic phase was separated
  8. dry with materialdried over Na2SO4
  9. filtrationAfter filtering
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by column chromatography on silica gel (eluted with DCM/MeOH=50:1 to 30:1)

Sources & evidence

ORD record
ord-5a9a6e73aedb46088c8fcd571d0a4892
Source dataset
uspto-grants-2016_09
Patent number
US09434733B2

Reaction notes

Loading…