4-Pyridinemethanamine → HCID 58102793, compound

HRID 450151Notes

Reaction equation

HRID 450151 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:25])[F:24])[N:3]=1.[NH2:26][CH2:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1>O1CCOCC1.O>[F:24][CH:23]([F:25])[C:15]1[N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([NH:26][CH2:27][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)[N:3]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=1

Participants

5

Reactant 2

HCID 773174-PyridinemethanamineHCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

Product 1

HCID 58102793HCID 58102793, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A stirred mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole (0.183 g, 0.5 mmol) and 4-aminomethylpyridine (0.135 g, 1.25 mmol) in 10 mL dioxane was heated under gentle reflux for 5 min, before being cooled and diluted with water. The mixture was extracted with CH2Cl2 and the organic layer was dried with Na2SO4. Chromatography on alumina, eluting with CH2Cl2/EtOAc (9:1), followed by chromatography on silica, eluting with CH2Cl2/EtOAc (3:2) gave 56 mg (26% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(4-pyridinylmethyl)-1,3,5-triazin-2-amine: mp 188-190° C.; 1H NMR (CDCl3) (rotamers) δ8.60 (br s, 2H), 8.42 and 8.13 (2d, J=7.4 and 8.0 Hz, 1H), 7.88 (m, 1H), 7.64 (t, JHF=53.6 Hz, 1H), 7.44-7.25 (m, 4H), 5.78 and 5.71 (2 m, exchangeable with D2O, 1H), 4.74 and 4.70 (2 d, J=6.0 and 6.0 Hz, 2H), 3.92-3.69 (m, 8H).

Workup

  1. temperaturewas heated
  2. temperatureunder gentle reflux for 5 min
  3. temperaturebefore being cooled
  4. extractionThe mixture was extracted with CH2Cl2
  5. dry with materialthe organic layer was dried with Na2SO4
  6. washChromatography on alumina, eluting with CH2Cl2/EtOAc (9:1)
  7. washeluting with CH2Cl2/EtOAc (3:2)

Sources & evidence

ORD record
ord-db5645feb33e4d56a353bbe29933a6fe
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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