6-Methoxy-3-pyridinylamine → HCID 49869353, compound

HRID 450166Notes

Reaction equation

HRID 450166 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([N-]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]=[C:39]([O:40][CH3:41])[C:34]=3[N:33]=[C:32]2[CH:42]([F:44])[F:43])[N:20]=1>C1COCC1.C(O)(=O)C.O>[F:44][CH:42]([F:43])[C:32]1[N:31]([C:21]2[N:22]=[C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:24]=[C:19]([NH:1][C:2]3[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=3)[N:20]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[C:39]([O:40][CH3:41])[C:34]=2[N:33]=1

Participants

7

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 2724682Lithium diisopropylamideHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole

Product 1

HCID 49869353HCID 49869353, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.310 g (2.50 mmol) of 5-amino-2-methoxypyridine in THF (3 mL) at 0° C. was added 1.35 mL of lithium diisopropylamide (2 M solution in benzene/heptanes/THF), and the mixture was stirred for 20 min. A solution of 0.240 g (0.61 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole in THF (5 mL) was added, and the resulting mixture was stirred for 1 hr at RT. After neutralization with acetic acid, the mixture was diluted with water and extracted with EtOAc. The organic layer was washed sequentially with water and aq. NH3, dried, and concentrated. Chromatography on alumina, eluting first with hexanes/EtOAc (1:1) and then with CH2Cl2/EtOAc (1:3) gave a reddish powder. Recrystallization from ethanol/CH2Cl2 gave 0.010 g (4% yield) of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-(6-methoxy-3-pyridinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 201-202° C.; 1H NMR (CDCl3) δ8.33 (br s, 1H), 7.93 (br s, 1H), 7.79 (dd, J=8.8, 2.7 Hz, 1H), 7.32-7.31 (m, 2H), 6.88-6.79 (m, 3H), 4.04 (s, 3H), 3.97 (s, 3H), 3.90 (s, 4H), 3.79 (s, 4H); Anal. Calcd. for C22H22F2N8O3: C, 54.5; H, 4.6; N, 23.1. Found: C, 54.6; H, 4.5; N, 22.9%.

Workup

  1. stirringthe resulting mixture was stirred for 1 hr at RT
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed sequentially with water and aq. NH3
  4. customdried
  5. concentrationconcentrated
  6. washChromatography on alumina, eluting first with hexanes/EtOAc (1:1)
  7. customwith CH2Cl2/EtOAc (1:3) gave a reddish powder
  8. customRecrystallization from ethanol/CH2Cl2

Sources & evidence

ORD record
ord-7a346835678d45c0a6a01b92768988b8
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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