2-Bromopropane → 2-Fluoro-9-isopropyl-N-((3-methylpyridin-2-yl)methyl)-9H-purin-6-amine

HRID 2047674Notes

Reaction equation

HRID 2047674 reaction equation
[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][CH2:12][C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:27]([CH3:29])[CH3:28].C(Cl)Cl.CCOCC.CO>CN(C)C=O>[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:27]([CH3:29])[CH3:28])=[C:4]([NH:11][CH2:12][C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[N:3]=1

Participants

6

Reactant 4

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 22565053DCM ether MeOHHCID 178426290HCID 178426290, compound

Product 1

HCID 592796442-Fluoro-9-isopropyl-N-((3-methylpyridin-2-yl)methyl)-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-fluoro-N-(3-methylpyridin-2-yl)methyl-9H-purin-6-amine (0.3 g, 1.17 mmol) in dimethylformamide (10 ml) at room temperature under an argon atmosphere, was added powdered, anhydrous K2CO3 (0.8 g, 5 eq, 5.85 mmol), followed by 2-bromopropane (1.15 ml, 11.7 mmol). The reaction mixture was stirred at room temperature for 24 h, when DCM:ether:MeOH (55:40:5), indicated that the reaction had gone to completion. The solvent was evaporated in vacuo and the residue partitioned between EtOAc (50 ml) and water (50 ml). The aqueous phase was extracted with more EtOAc (2×50 ml) and the combined organic phase washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by silica gel column chromatography, eluted with CHCl3:MeOH (98:2) to afford the title compound as a slightly yellow film (170 mg, 48%). δH (CDCl3, 500 MHz) 1.51 (6 H, d, J 7.5, CH[CH3]2), 2.28 (3 H, s, CH3), 4.68-4.65 (3H, m, NHCH2 and CHMe2), 7.08-7.05 (1 H, m, ArH), 7.4 (1 H, d, J 5, ArH), 7.72 (1 H, s, ArH), 7.93 (1H, s, br, NH), 8.34 (1 H, d, J 5, ArH); δC (CDCl3, 500 MHz) 160.09 (C), 158.43 (C), 155.97 (C), 154.06 (C), 145.85 (CH), 137.73 (CH), 137.54 (CH), 130.67 (C), 122.28 (CH), 118.73 (C), 47.28 (CH), 42.87 (CH2), 22.43 (2×CH3), 17.66 (CH3); 19F NMR δ −50.20; m/z 301.2 (M+H)

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between EtOAc (50 ml) and water (50 ml)
  3. extractionThe aqueous phase was extracted with more EtOAc (2×50 ml)
  4. washthe combined organic phase washed with brine (50 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluted with CHCl3:MeOH (98:2)

Sources & evidence

ORD record
ord-7cd4af2a88b846e4a7541ae95282987b
Source dataset
uspto-grants-2013_11
Patent number
US08592581B2

Reaction notes

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