Diisopropylethylamine → HCID 25020438, compound

HRID 2047679Notes

Reaction equation

HRID 2047679 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][CH:32]([CH2:39][CH3:40])[CH:33]([OH:38])[C:34]([F:37])([F:36])[F:35]>CCCCO.CS(C)=O>[F:35][C:34]([F:37])([F:36])[CH:33]([OH:38])[CH:32]([NH:31][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)[CH2:39][CH3:40]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 107256073-Amino-1,1,1-trifluoropentan-2-olHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amine

Product 1

HCID 25020438HCID 25020438, compound

Reagents, catalysts & solvents 1

HCID 20476217n-BuOH DMSOSolvent

Procedure

To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (300 mg, 1.05 mmol) in n-BuOH/DMSO (5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (1.4 ml, 10 eq, 8 mmol) followed by 3-amino-1,1,1-trifluoropentan-2-ol (1 g, 6.4 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 EtOAc (50 ml) and water (50 ml), the aqueous phase was extracted with more EtOAc (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 title compound as a colorless film (42 mg, 9.4%). δH (CDCl3, 500 MHz) 1.04 (3 H, t, J 7.5, CHCH2CH3) 1.56 (6 H, d, J 7.5, CH[CH3]2), 1.8-1.73 (2 H, m, CHCH2CH3), 4.13-4.07 (1 H, m, CHMe2), 4.22-4.2 (1 H, m, CHEt) 4.57-4.55 (1 H, m, CHOHCF3), 4.71 (2 H, s, b, NHCH2Ar), 5.08 (1 H, s, b, NH), 7.2 (1 H, dd, J 5, 10 ArH), 7.51 (1 H, s, ArH), 7.64 (1 H, d, J 10, ArH), 8.46 (1 H, d, J 5, ArH), 8.55 (1 H, s, ArH); δC (CDCl3, 500 MHz) 159.28 (C), 154.72 (C), 149.07 (CH), 148.47 (CH), 135.44 (CH), 134.83 (C), 134.48 (CH), 124.12 (C), 123.44 (CH), 114.62 (C), 73.1 (CH), 55.88 (CH), 46.70 (CH), 41.78 (CH2), 23.68 (CH2) 22.36 (2×CH3), 11.55 (CH3); 19FNMR δ −74.83; m/z 424.2 (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 EtOAc (50 ml) and water (50 ml)
  5. extractionthe aqueous phase was extracted with more EtOAc (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-eddfd265d9ca4e9eabf6280589b875fd
Source dataset
uspto-grants-2013_11
Patent number
US08592581B2

Reaction notes

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