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

HRID 2047658Notes

Reaction equation

HRID 2047658 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[CH:14]=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=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[CH:14]=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=2)[N:3]=1

Participants

6

Reactant 4

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 22565053DCM ether MeOHHCID 178425512HCID 178425512, compound

Product 1

HCID 592796362-Fluoro-9-isopropyl-N-((6-methylpyridin-3-yl)methyl)-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-fluoro-N-(6-methylpyridin-3-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 (100 ml) and water (100 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 flash column chromatography, eluted with CHCl3:MeOH (98:2) to afford the title compound as a slightly yellow film (195 mg, 55%). δH (CDCl3, 250 MHz) 1.52 (6 H, d, J 7.5, CH[CH3]2), 2.5 (3 H, s, CH3), 4.76-4.6 (3 H, m, NHCH2 and CHMe2), 7.06 (1 H, d, J 2.5, ArH), 7.35 (1 H, s, br, NH), 7.56 (2 H, s, br, ArH), 8.47 (1 H, s, br, ArH); δC (CDCl3, 250 MHz) 157.6 (C), 156.32 (C), 156 (C), 148.47 (CH), 137.72 (CH), 136.08 (CH), 130.83 (C), 123.11 (CH), 118.2 (C), 47.38 (CH), 43.2 (CH2), 23.99 (CH3), 22.5 (2×CH3); m/z 301.2 (M+H)

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between EtOAc (100 ml) and water (100 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 flash column chromatography
  8. washeluted with CHCl3:MeOH (98:2)

Sources & evidence

ORD record
ord-968e1434b45846c5a1b71213b0b8fa84
Source dataset
uspto-grants-2013_11
Patent number
US08592581B2

Reaction notes

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