Potassium Carbonate → HCID 58711997, compound

HRID 2374960Notes

Reaction equation

HRID 2374960 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]1(/[CH:37]=[CH:38]/[C:39]([NH2:41])=[O:40])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1>[CH3:30][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2](/[C:37](/[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:38]\[C:39]([NH2:41])=[O:40])[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

8

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 5273472trans-CinnamamideHCID 112135557-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amine

Product 1

HCID 58711997HCID 58711997, compoundYield 19.7%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

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) (40 mg, 0.085 mmol), (2E)-3-phenylprop-2-enamide (15.0 mg, 0.10 mmol), tetrakis(triphenylphosphine) palladium (0) (5.0 mg, 0.004 mmol) and potassium carbonate (17.6 mg, 0.127 mmol) was added 1,4-dioxane (1.0 mL). In a sealed reaction vessel, the mixture was heated with microwave radiation at 110° C. for 20 minutes. Analysis by LCMS indicated that no reaction occurred. To the mixture was added diisopropylethylamine (0.044 mL, 0.255 mmol), Combiphos catalyst POPd (Dihydrogen dichlorobis(di-tert-butylphosphinito-κP)palladate(2-)) (5.0 mg, 0.01 mmol) and tetrabutylammonium bromide (5.0 mg, 0.015 mmol) and heated with microwave radiation at 130° C. for 70 minutes. After cooling to room temperature, removed solvent under reduced pressure, dissolved residue in methanol (25 mL), and added silica gel (200 mg). Following 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 ethylacetate:methanol (100:0 to 80:20) using a RediSep silica gel cartridge (4.2 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give a gold oil. Added diethyl ether (15 mL) to precipitate, and vacuum filtered to give (2Z)-3-(3-{5-methyl-2-[(3,4,5-trimethoxyphenyl)amino]imidazo[5,1-f][1,2,4]triazin-7-yl}phenyl)-3-phenylprop-2-enamide (0.009 g) as a yellow solid. 1H NMR (CDCl3): δ8.80 (s, 1H), 8.48-8.46 (m, 1H), 7.40-7.28 (m, 7H), 7.17-7.15 (m, 1H), 7.02 (s, 1H), 6.89-6.86 (m, 2H), 6.44 (m, 1H), 5.34 (s, 2H), 3.83-3.79 (m, 9H), 2.60-2.57 (m, 3H). MS m/z 537 (M+1).

Workup

  1. customIn a sealed reaction vessel
  2. temperatureheated with microwave radiation at 130° C. for 70 minutes
  3. temperatureAfter cooling to room temperature
  4. customremoved solvent under reduced pressure
  5. dissolutiondissolved residue in methanol (25 mL)
  6. additionadded silica gel (200 mg)
  7. customevaporation of the volatiles under reduced pressure
  8. washsubjected to a gradient elution
  9. concentrationconcentrated under reduced pressure
  10. customto give a gold oil
  11. customAdded diethyl ether (15 mL) to precipitate
  12. filtrationvacuum filtered

Sources & evidence

ORD record
ord-2dddf95097204a269eb4ac7bae26a82f
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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