3-Amino-2-methylpyridine → HCID 136639890, compound

HRID 1748797Notes

Reaction equation

HRID 1748797 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH:12]1[S:18][CH2:17][CH2:16][NH:15][C:14]2[N:19]([CH3:28])[N:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:13]1=2)[C:5](OC)=[O:6].[NH2:29][C:30]1[C:31]([CH3:36])=[N:32][CH:33]=[CH:34][CH:35]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH:12]1[S:18][CH2:17][CH2:16][NH:15][C:14]2[N:19]([CH3:28])[N:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:13]1=2)[C:5]([NH:29][C:30]1[C:31]([CH3:36])=[N:32][CH:33]=[CH:34][CH:35]=1)=[O:6]

Participants

5

Reactant 3

HCID 5726163-Amino-2-methylpyridineHCID 2733832Lithium HexamethyldisilazideHCID 136216170HCID 136216170, compound

Product 1

HCID 136639890HCID 136639890, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of methyl 3-methyl-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzoate (0.20 g, 0.51 mmol) and 3-amino-2-methylpyridine (0.066 g, 0.61 mmol) in anhydrous THF (20 mL), was added lithium bis(trimethylsilyl)amide solution (1.01 mL, 1 M in THF, 1.01 mmol), at about −60° C. The resulting mixture was stirred for about 30 min, during which time the temperature was allowed to rise from about −60° C. to about 0° C., and then quenched by the addition of water (20 mL), while keeping the temperature below 0° C. The resulting mixture was extracted with ethyl acetate (60 mL). The organic layer was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate) to afford 3-methyl-N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide (0.10 g, 0.21 mmol, 42%) as a beige foam: LC-MS (Table 1, Method a) Rt=1.85 min, m/z 471 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.56 (3H, s) 2.72 (3H, s) 2.67-2.75 (1H, m) 2.87 (1H, ddd, J=15.0, 9.3, 2.6 Hz) 3.29 (1H, ddd, J=13.3, 9.3, 2.5 Hz) 3.65 (1H, ddd, J=13.3, 6.2, 2.3 Hz) 3.85 (3H, s) 3.87 (1H, br s) 6.76 (1H, s) 7.08 (1H, ddd, J=7.4, 4.9, 1.1 Hz) 7.20 (1H, dd, J=8.1, 4.7 Hz) 7.35 (1H, t, J=8.0 Hz) 7.55 (1H, dd, J=8.0, 2.0 Hz) 7.60 (1H, td, J=7.8, 1.8 Hz) 7.62 (1H, d, J=1.8 Hz) 7.69 (1H, br s) 7.84 (1H, dt, J=8.0, 1.0 Hz) 8.30 (1H, dd, J=4.8, 1.6 Hz) 8.35 (1H, dd, J=8.1, 1.4 Hz) 8.47 (1H, ddd, J=4.8, 1.7, 0.8 Hz).

Workup

  1. customat about −60° C
  2. customto rise from about −60° C. to about 0° C.
  3. customquenched by the addition of water (20 mL)
  4. customthe temperature below 0° C
  5. extractionThe resulting mixture was extracted with ethyl acetate (60 mL)
  6. washThe organic layer was washed with brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by column chromatography (SiO2, ethyl acetate)

Sources & evidence

ORD record
ord-fd6fbd513aaf4748b94e45bf8301f578
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

Loading…