Acrylamide → HCID 58711931, compound

HRID 2374895Notes

Reaction equation

HRID 2374895 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:16]3[C:11]([CH:12]=[N:13][C:14]([NH:17][C:18]4[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=4)=[N:15]3)=[C:10]([CH3:30])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:31]([NH2:35])(=[O:34])[CH:32]=[CH2:33].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:30][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2](/[CH:33]=[CH:32]/[C:31]([NH2:35])=[O:34])[CH:7]=[CH:6][CH:5]=2)[N:16]2[C:11]=1[CH:12]=[N:13][C:14]([NH:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=1)=[N:15]2

Participants

7

Reactant 4

HCID 6579AcrylamideHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 112135557-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amine

Product 1

HCID 58711931HCID 58711931, compoundYield 8.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture of 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (Example 9) (0.054 g, 0.12 mmol), acrylamide (0.025 g, 0.35 mmol), palladium (II) acetate (2.7 mg, 0.012 mmol) and tris(o-tolyl)phosphine (7.3 mg, 0.024 mmol) in acetonitrile (1 mL) was added triethylamine (0.050 mL, 0.35 mmol). The solution was heated to reflux for 30 minutes. After cooling to room temperature, the solution was filtered, and silica gel (1 g) was added, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexanes (50:50) to ethyl acetate:hexanes (100:0) to ethyl acetate:methanol (99:1) using a RediSep silica gel cartridge (4 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give (2E)-3-(3-{5-methyl-2-[(3,4,5-trimethoxyphenyl)amino]-imidazo[5,1-f][1,2,4]triazin-7-yl}phenyl)prop-2-enamide (0.0046 g) as a yellow solid. 1H NMR (CD3OD): δ9.05 (s, 1H), 8.49 (s, 1H), 8.37 (d, J=7.3 Hz, 1H), 7.67-7.51 (m, 4H), 7.05 (s, 2H), 6.68 (d, J=15.9 Hz, 1H) 3.74 (s, 3H), 3.72 (s, 6H), 2.60 (s, 3H). MS m/z 461 (M+1).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 30 minutes
  3. filtrationthe solution was filtered
  4. additionsilica gel (1 g) was added
  5. customfollowed by evaporation of the volatiles under reduced pressure
  6. washsubjected to a gradient elution
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7767d865e30e41bd9872167f97516f0d
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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