2-Pyridinemethanamine → HCID 178506015, compound

HRID 1432382Notes

Reaction equation

HRID 1432382 reaction equation
Cl[C:2]1[N:10]=[C:9]([F:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.[NH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1>C(Cl)(Cl)Cl.CO>[F:11][C:9]1[N:8]=[C:7]2[C:3]([N:4]=[CH:5][NH:6]2)=[C:2]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:10]=1

Participants

4

Reactant 2

HCID 195092-PyridinemethanamineHCID 178506011HCID 178506011, compound

Product 1

HCID 178506015HCID 178506015, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 6-chloro-2-fluoro-9H-purine (prepared according to Gray, N. S.; Kwon, S.; Schultz, P. G. Tetrahedron Lett 1997, 38, 1161-1164; 0.4 g, 2.31 mmol) in BunOH (25 mL) under Ar, cooled to 0° C., was added Pri2NEt (1.13 mL, 6.49 mmol) followed by 2-(aminomethyl)pyridine (0.48 mL, 4.66 mmol). The reaction mixture was stirred at 0° C. for 3 h, and then allowed to return to RT over 30 min. and stirred at this temperature for 1 h, when TLC (9:1 CHCl3/MeOH) indicated that the reaction had gone to completion. The solvent was evaporated in vacuo and the residue partitioned between citric acid solution (200 mL, 10% aq) and EtOAc (200 mL), the aqueous phase was separated and extracted with more EtOAc (2×100 mL). The pH of the aqueous phase was adjusted to 7.0 with NaOH solution (50% w/v, aq), extracted with EtOAc (4×100 mL), and the bulked organic phase was washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient column chromatography on silica gel, eluted with CHCl3/MeOH (95:5→85:15), to afford the title compound as a light yellow solid (0.40 g, 71%). Mp 217-220° C. 1H-NMR (d6-DMSO, 250 MHz): δ 4.58 (d, 2H, J=5.68 Hz, —HNCH2-Pyr), 7.29, 7.71, 8.49 (3×m, 4H, Pyr), 8.10 (s, 1H, —N═CH—NH—), 8.69 (bs, 1H, —HNCH2-Pyr), 13.07 (bs, 1H, —N═CH—NH—). FAB-MS m/z (relative intensity): 245 ([M+H]+, 55), 176 (30), 154 (100), 136 (85). Accurate Mass (M+H): Actual: 245.0951, Measured: 245.0942. Microanalysis (Expected:Measured) C11H9N6F.0.4H2O: C, 52.55:52.91; H, 3.93:3.49; N, 33.42:33.26.

Workup

  1. additionwas added Pri2NEt (1.13 mL, 6.49 mmol)
  2. waitto return to RT over 30 min.
  3. stirringstirred at this temperature for 1 h
  4. customThe solvent was evaporated in vacuo
  5. customthe residue partitioned between citric acid solution (200 mL, 10% aq) and EtOAc (200 mL)
  6. customthe aqueous phase was separated
  7. extractionextracted with more EtOAc (2×100 mL)
  8. extractionextracted with EtOAc (4×100 mL)
  9. washthe bulked organic phase was washed with brine (50 mL)
  10. dry with materialdried (MgSO4)
  11. customevaporated in vacuo
  12. customThe residue was purified by gradient column chromatography on silica gel
  13. washeluted with CHCl3/MeOH (95:5→85:15)

Sources & evidence

ORD record
ord-740ec925d53f4519bc193ac45af79c2c
Source dataset
uspto-grants-2009_11
Patent number
US07612079B2

Reaction notes

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