Acetic Acid → HCID 58102789, compound

HRID 450152Notes

Reaction equation

HRID 450152 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl[C:19]1[N:24]=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:22]=[C:21]([N:31]2[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[N:33]=[C:32]2[CH:40]([F:42])[F:41])[N:20]=1.C(O)(=O)C>C1COCC1.O>[F:42][CH:40]([F:41])[C:32]1[N:31]([C:21]2[N:22]=[C:23]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:24]=[C:19]([NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[N:20]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[N:33]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 104392-AminopyridineHCID 2733832Lithium HexamethyldisilazideHCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

Product 1

HCID 58102789HCID 58102789, compoundYield 13.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 0.224 g (2.38 mmol) of 2-aminopyridine in THF (3 mL) was added 2.5 mL of lithium bis(trimethylsilyl)amide (1 M solution in THF) and the mixture was stirred for 10 min. A solution of 0.204 g (0.56 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in THF (4 mL) was added and the mixture was stirred for 1 hr. The resulting mixture was neutralized with acetic acid, diluted with water and extracted with EtOAc. The organic layer was washed with water and aqueous NH3, and dried. After removal of the solvent, the residue was purified by chromatography on alumina, eluting with CH2Cl2/EtOAc (1:5) to give an orange powder. Recrystallization from EtOH/CH2Cl2 gave 31.5 mg (13% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(2-pyridinyl)-1,3,5-triazin-2-amine: mp 230-232° C.; 1H NMR (CDCl3) δ 8.41-8.37 (m, 2H), 8.20 (d, J=8.4 Hz, 1H), 8.12 (br s, 1H), 7.91-7.89 (m, 1H), 7.75 (td, J=7.5, 1.8 Hz, 1H), 7.60 (t, JHF=53.5 Hz, 1H), 7.45-7.39 (m, 2H), 7.05 (ddd, J=7.3, 4.9, 0.9 Hz, 1H), 3.96-3.94 (m, 4H), 3.85-3.82 (m, 4H); HRMS (FAB+) MNa+ Calcd. for C20H18F2N8NaO: m/z 447.1466. Found: m/z 447.1464.

Workup

  1. stirringthe mixture was stirred for 1 hr
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water and aqueous NH3
  4. customdried
  5. customAfter removal of the solvent
  6. customthe residue was purified by chromatography on alumina
  7. washeluting with CH2Cl2/EtOAc (1:5)
  8. customto give an orange powder
  9. customRecrystallization from EtOH/CH2Cl2

Sources & evidence

ORD record
ord-cb3c57ecabeb43b7903a7628aa3a3340
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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