1,2-Dimethoxyethane → HCID 11156498, compound

HRID 2374957Notes

Reaction equation

HRID 2374957 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.OB(O)[C:33]1[CH:34]=[C:35]([CH:39]=[CH:40][CH:41]=1)[C:36]([OH:38])=[O:37].C(=O)([O-])[O-].[K+].[K+].COCCOC>ClCCl.[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>[CH3:30][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([C:33]3[CH:41]=[CH:40][CH:39]=[C:35]([C:36]([OH:38])=[O:37])[CH:34]=3)[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 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 112135557-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amine

Product 1

HCID 11156498HCID 11156498, compoundYield 64.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolvent

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) (25 mg, 0.05 mmol), 3-(dihydroxyboryl)benzoic acid (10.6 mg, 0.06 mmol), tetrakis(triphenylphosphine) palladium (0) (3.1 mg, 0.003 mmol) and potassium carbonate (11.0 mg, 0.08 mmol) was added DME (0.9 mL) and distilled water (0.3 mL). In a sealed reaction vessel, the mixture was heated with microwave radiation at 110° C. for 20 minutes. After cooling to room temperature, removed solvent under reduced pressure, dissolved residue in dichloromethane and methanol, 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 dichloromethane: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 solid that was suspended in dichloromethane and vacuum filtered to give 3′-{5-methyl-2-[(3,4,5-trimethoxyphenyl)amino]imidazo[5,1-f][1,2,4]triazin-7-yl}-1,1′-biphenyl-3-carboxylic acid (0.0164 g) as a yellow solid. 1H NMR (DMSO-d6): δ9.63 (s, 1H), 9.26 (s, 1H), 8.57-8.53 (m, 2H), 8.21 (s, 1H), 7.95-7.92 (m, 2H), 7.78 (d, J=6.2 Hz, 1H), 7.62-7.55 (m, 2H), 7.07 (s, 2H), 3.63 (s, 6H), 3.58 (s, 3H), 2.55 (s, 3H). MS m/z 512 (M+1).

Workup

  1. distillationdistilled water (0.3 mL)
  2. customIn a sealed reaction vessel
  3. temperatureAfter cooling to room temperature
  4. customremoved solvent under reduced pressure
  5. dissolutiondissolved residue in dichloromethane
  6. additionmethanol, and added 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 solid
  11. filtrationvacuum filtered

Sources & evidence

ORD record
ord-9ce1665b458740e1abb611d75272279b
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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