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

HRID 243424Notes

Reaction equation

HRID 243424 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1.Cl[C:21]1[C:26]2=[N:27][CH:28]=[CH:29][N:25]2[N:24]=[CH:23][N:22]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C.CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:12][C:21]3[C:26]4=[N:27][CH:28]=[CH:29][N:25]4[N:24]=[CH:23][N:22]=3)[CH3:11])[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 457897354-Chloroimidazo(2,1-f)(1,2,4)triazineHCID 68157234(S)-1-(6-Fluoro-1-pyrid-2-yl-1H-benzoimidazol-2-yl)ethylamine

Product 1

HCID 68158020[(S)-1-(6-Fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)-ethyl]-imidazo[2,1-f][1,2,4]triazin-4-yl-amineYield 63.7%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(6-Fluoro-1-pyrid-2-yl-1H-benzoimidazol-2-yl)ethylamine (0.066 g, 0.26 mmol), 4-chloroimidazo[2,1-f][1,2,4]triazine (WO2010/014930) (0.040 g, 0.26 mmol) and diisopropylethylamine (0.090 mL, 0.52 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 322 as a white solid, (62 mg, 63%). LCMS (Method C): RT 3.78 min [M+H]+ 375.04. 1H NMR δ (ppm) (DMSO-d): 9.13 (1H, d, J=7.61 Hz), 8.57 (1H, dd, J=4.90, 1.81 Hz), 8.01-7.98 (2H, m), 7.93 (1H, s), 7.74-7.73 (2H, m), 7.55 (1H, d, J=1.12 Hz), 7.44-7.44 (1H, m), 7.15-7.15 (2H, m), 5.92 (1H, dq, J=7.11 Hz), 1.65 (3H, d, J=6.87 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-8023e3f1aff5430d828c61197c9116c2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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