5-Amino-2-chloropyridine → HCID 58102798, compound

HRID 450168Notes

Reaction equation

HRID 450168 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Li])CCC.Cl[C:15]1[N:20]=[C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:18]=[C:17]([N:27]2[C:31]3[CH:32]=[CH:33][CH:34]=[C:35]([O:36][CH3:37])[C:30]=3[N:29]=[C:28]2[CH:38]([F:40])[F:39])[N:16]=1>C1COCC1.C(O)(=O)C.O>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][C:15]2[N:16]=[C:17]([N:27]3[C:31]4[CH:32]=[CH:33][CH:34]=[C:35]([O:36][CH3:37])[C:30]=4[N:29]=[C:28]3[CH:38]([F:40])[F:39])[N:18]=[C:19]([N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[N:20]=2)=[CH:3][CH:4]=1

Participants

7

Reactant 3

HCID 793055-Amino-2-chloropyridineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 178418339Butyllithium

Product 1

HCID 58102798HCID 58102798, compoundYield 5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 0.246 g (1.92 mmol) of 5-amino-2-chloropyridine in THF (4 mL) was added 0.85 mL of n-butyllithium (2.5 M solution in hexanes), and the mixture was stirred for 10 min. A solution of 0.260 g (0.66 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) in THF (5 mL) was added. The resulting mixture was stirred at room temperature for 1 hr. After neutralization with acetic acid, the mixture was diluted with water and extracted with EtOAc. The organic layer was washed successively with water and aqueous NH3, and dried. Removal of the solvent and chromatography of the residue on alumina eluting first with hexanes/EtOAc (1:1) and then with CH2Cl2-EtOAc (1:5) gave a brown powder. Recrystallization from ethanol/CH2Cl2 gave 0.016 g (5% yield) of N-(6-chloro-3-pyridinyl)-4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 260-262° C.; 1H NMR (CDCl3) δ8.69 (s, 1H), 7.95-7.90 (m, 2H), 7.48 (t, J=53.5 Hz, 1H), 7.37-7.33 (m, 2H), 7.11 (s, 1H), 6.83 (d, J=8.0 Hz, 1H), 4.05 (s, 3H), 3.94-3.87 (m, 4H), 3.81 (m, 4H); Anal. Calcd. for C21H19ClF2N8O2: C, 51.6; H, 3.9; N, 22.9; Cl, 7.25. Found: C, 52.1; H, 3.9; N, 22.5; Cl, 7.1%.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1 hr
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed successively with water and aqueous NH3
  4. customdried
  5. customRemoval of the solvent and chromatography of the residue on alumina eluting first with hexanes/EtOAc (1:1)
  6. customwith CH2Cl2-EtOAc (1:5) gave a brown powder
  7. customRecrystallization from ethanol/CH2Cl2

Sources & evidence

ORD record
ord-86d5a85690f74185918d93aea1f463a8
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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