Diisopropylethylamine → [(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-imidazo[2,1-f][1,2,4]triazin-4-yl-amine

HRID 243423Notes

Reaction equation

HRID 243423 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.Cl[C:23]1[C:28]2=[N:29][CH:30]=[CH:31][N:27]2[N:26]=[CH:25][N:24]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C.CCOC(C)=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:23]3[C:28]4=[N:29][CH:30]=[CH:31][N:27]4[N:26]=[CH:25][N:24]=3)[CH3:13])[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]=2[CH:21]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 457897354-Chloroimidazo(2,1-f)(1,2,4)triazineHCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 68158019[(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-imidazo[2,1-f][1,2,4]triazin-4-yl-amineYield 78.7%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.106 g, 0.32 mmol), 4-chloroimidazo[2,1-f][1,2,4]triazine (WO2010/014930) (0.050 g, 0.32 mmol) and diisopropylethylamine (0.222 mL, 1.28 mmol) in isopropanol (2 mL) was heated to 60° C. in a sealed tube for 0.5 h. The reaction mixture was cooled and diluted with EtOAc (20 mL) and washed with water (2 mL) The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM). Product containing fractions were evaporated and freeze dried to give 321 as a pale pink solid, (94 mg, 78%). LCMS (Method C): RT 4.31 min [M+H]+ 374.01. 1H NMR δ (ppm) (DMSO-d): 9.15 (1H, d, J=7.24 Hz), 8.02 (1H, d, J=1.09 Hz), 7.95 (1H, s), 7.71 (1H, dd, J=8.81, 4.85 Hz), 7.57-7.54 (3H, m), 7.48-7.39 (3H, m), 7.10 (1H, td, J=9.33, 2.51 Hz), 6.83 (1H, dd, J=8.91, 2.52 Hz), 5.57 (1H, dq, J=7.00 Hz), 1.61 (3H, d, J=6.88 Hz)

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with water (2 mL) The organic extracts
  3. dry with materialwere dried (Na2SO4)
  4. customevaporated to dryness
  5. custompurified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM)
  6. additionProduct containing fractions
  7. customwere evaporated
  8. customfreeze dried

Sources & evidence

ORD record
ord-07c5b0085d43441b926ab49ca3f8bbc2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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