Diisopropylethylamine → HCID 57433122, compound

HRID 2047675Notes

Reaction equation

HRID 2047675 reaction equation
F[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][CH2:32][C@H:33]([OH:35])[CH3:34]>CCCCO.CS(C)=O>[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH:31][CH2:32][C@H:33]([OH:35])[CH3:34])=[N:3][C:4]=2[NH:14][CH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 439938(2R)-1-aminopropan-2-olHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amine

Product 1

HCID 57433122HCID 57433122, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 20476217n-BuOH DMSOSolvent

Procedure

To a stirred solution of 2-fluoro-9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]purine (300 mg, 1.05 mmol) in n-BuOH/DMSO (5 ml, 4:1) at room temperature under an argon atmosphere was added DIEA (2 ml, 10 eq, 10.5 mmol) followed by (R)-1-aminopropan-2-ol (395 mg, 5.25 mmol). The flask was fitted with a condenser and the reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 72 h. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate (50 mL) and water (50 mL), the aqueous phase was extracted with more ethyl acetate (2×25 mL), and the combined organic phase was washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient flash column chromatography on silica gel eluted with CHCl3:MeOH (100:0→95:5), to afford the pure product as a colorless oil (38 mg, 10.6%). δH (250 MHz, CDCl3) 1.15 (3 H, d, J 7.5, CHCH3OH), 1.45 (6 H, d, J 7.5, CH[CH3]2), 3.3-3.2 (1 H, m, NHCHHCHMeOH)), 3.45-3.36 (1 H, m, NHCHHCHMeOH), 3.96-3.9 (1 H, m, CHMe2), 4.58-4.47 (1 H, m, CHMeOH), 4.69 (2 H, d, J 5, NHCH2Ar), 5.23 (1 H, t, J 5, NHCH2CHMeOH), 6.32 (1 H, s, br, NHCH2Ar), 7.16-7.11 (1 H, m, ArH), 7.4 (1 H, s, ArH), 7.6 (1 H, d, J 7.5, ArH), 8.4 (1 H.d, J 2.5, ArH), 8.55 (1 H, s, ArH); δC (250 MHz, CDCl3) 160.07 (C), 154.95 (C), 154.7 (C), 151.1 (C), 149.27 (CH), 148.54 (CH), 135.3 (CH), 134.73 (CH), 123.39 (CH), 114.61 (C), 68.83 (CH), 50.09 (CH2), 46.49 (CH), 41.95 (CH2), 22.49 (2×CH3), 20.85 (CH3); m/z 342.2 (M+H)

Workup

  1. customThe flask was fitted with a condenser
  2. customthe reaction mixture was placed in a preheated oil bath at 140° C.
  3. customthe solvent was evaporated in vacuo
  4. customThe residue was partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. extractionthe aqueous phase was extracted with more ethyl acetate (2×25 mL)
  6. washthe combined organic phase was washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was purified by gradient flash column chromatography on silica gel
  10. washeluted with CHCl3:MeOH (100:0→95:5)

Sources & evidence

ORD record
ord-429b454e1d0a44febf609b5955b01ed2
Source dataset
uspto-grants-2013_11
Patent number
US08592581B2

Reaction notes

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