Binap, (A+-)- → HCID 58711965, compound

HRID 2374965Notes

Reaction equation

HRID 2374965 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.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]2[CH:45]=[CH:44][C:42]([NH2:43])=[CH:41][CH:40]=2)[CH2:34][CH2:33]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>CO.C(OCC)(=O)C.O1CCOCC1>[CH3:30][C:10]1[N:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:43][C:42]3[CH:41]=[CH:40][C:39]([CH2:38][N:35]4[CH2:34][CH2:33][N:32]([CH3:31])[CH2:37][CH2:36]4)=[CH:45][CH:44]=3)[CH:3]=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 634876Binap, (A+-)-HCID 31539964-((4-Methylpiperazin-1-yl)methyl)anilineHCID 112135557-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amineHCID 23676156Sodium t-butoxide

Product 1

HCID 58711965HCID 58711965, compoundYield 41.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °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), 4-[(4-methylpiperazin-1-yl)methyl]aniline (20.9 mg, 0.102 mmol), (S)-(−)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl ((S)-BINAP) (15.9 mg, 0.026 mmol), Tris(dibenzylidineacetone)dipalladium (0) (7.8 mg, 0.008 mmol) and sodium t-butoxide (11.4 mg, 0.12 mmol) was added 1,4-dioxane (1.5 mL). In a sealed reaction vessel, the mixture was heated with microwave radiation at 140° C. for 60 minutes. After cooling to room temperature, diluted mixture with methanol (5 mL) and ethyl acetate (5 mL) followed by filtration over celite. Removed solvent under reduced pressure and diluted brown residue in DMSO (1.0 mL). Injected (2×0.5 mL) on an Agilent reverse phase prep LC subjected to a gradient elution using acetonitrile(0.1% Formic acid):water(0.1% Formic acid) (10:90 to 90:10). The appropriate fractions were combined and concentrated under reduced pressure to give 5-methyl-7-[3-({4-[(4-methylpiperazin-1-yl)methyl]phenyl}amino)phenyl]-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (0.021 g) as a yellow solid. 1H NMR (CDCl3): δ8.78 (s, 1H), 8.47 (s, 1H), 8.09 (dd, J=1.9, 1.8 Hz, 1H), 8.0-7.98 (m, 1H), 7.33 (dd, J=7.9, 7.8 Hz, 1H), 7.19 (ddd, J=7.9, 2.2, 0.8 Hz, 1H), 7.16-7.14 (m, 2H), 7.11 (s, 1H), 7.07-7.05 (m, 2H), 6.94 (m, 2H), 3.82 (s, 9H), 3.53 (s, 2H), 2.90-2.54 (m, 14H). MS m/z 595 (M+1).

Workup

  1. customIn a sealed reaction vessel
  2. temperatureAfter cooling to room temperature
  3. filtrationfollowed by filtration over celite
  4. additionRemoved solvent under reduced pressure and diluted brown residue in DMSO (1.0 mL)
  5. washsubjected to a gradient elution
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-72cc375aa71049a4ba21ade7150b7fdd
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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