Ammonium Hydroxide → 1,1,1,3,3,3-Hexafluoro-2-((9-isopropyl-6-(pyridine-3-ylmethylamino)-9H-purin-2-ylamino)methyl)propan-2-ol

HRID 2047680Notes

Reaction equation

HRID 2047680 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.C(N(C(C)C)CC)(C)C.[NH2:31][CH2:32][C:33]([OH:42])([C:38]([F:41])([F:40])[F:39])[C:34]([F:37])([F:36])[F:35].[OH-].[NH4+].FC(F)(F)C1(C(F)(F)F)CO1>CCCCO.CS(C)=O>[F:35][C:34]([F:36])([F:37])[C:33]([CH2:32][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)([OH:42])[C:38]([F:39])([F:41])[F:40]

Participants

7

Reactant 5

HCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 114694192,2-Bis(trifluoromethyl)oxiraneHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amineHCID 120236773-Amino-1,1,1-trifluoro-2-(trifluoromethyl)propan-2-ol2×

Product 1

HCID 250205381,1,1,3,3,3-Hexafluoro-2-((9-isopropyl-6-(pyridine-3-ylmethylamino)-9H-purin-2-ylamino)methyl)propan-2-olYield 23%

Reagents, catalysts & solvents 1

HCID 20476217n-BuOH DMSOSolvent

Procedure

To a stirred solution of 2-fluoro-9-isopropyl-6-[(pyridine-3-ylmethyl)-amino]purine (50 mg, 0,175 mmol) in n-BuOH/DMSO (2.5 ml, 4:1) at room temperature and under an argon atmosphere was added diisopropylethylamine (135 mg, 1.05 mmol) followed by 2-(aminomethyl)-1,1,1,3,3,3-hexafluoropropane-2-ol (prepared from the reaction of 30% ammonium hydroxide with 2,2-bis[trifluoromethyl]oxirane). The reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 3 days. The reaction was followed by LCMS and was gone by only 30%. Additional newly prepared 2-(aminomethyl)-1,1,1,3,3,3-hexafluoropropane-2-ol was added and the reaction continued. This addition was done on three more consecutive days to achieve complete conversion. After removal of solvent, the residue was purified by silica gel flash column chromatography to give the title compound as a pale brown powder (19 mg, 23%); δH (CDCl3, 500 MHz) 1.57 (6 H, d, J 7.5, CH[CH3]2), 3.48-3.44 (1 H, m, NHCHHCOH[CF3]2, 3.86-3.81 (1 H, m, NHCHHCOH[CF3]2, 4.62-4.555 (1 H, m, CHMe2), 4.78-4.74 (2 H, m, NHCH2ArH), 5.35 (1H, s, br, OH), 6.36 (1 H, s, br, NH), 7.27-7.22 (2 H, m, ArH), 7.7-7.67 (1 H, m, ArH), 8.5 (1 H, d, J 5, ArH), 8.66 (1 H, s, ArH); δC (CDCl3, 500 MHz) 159.99 (C), 154.63 (C), 149.53 (C), 149.05 (C), 148.6 (CH), 137.79 (C), 135.41 (C), 135.38 (CH), 135 (CH), 123.44 (CH), 75.03 (C), 47.62 (CH2), 46.84 (CH), 42.05 (CH2), 22.1 (2×CH3); m/z 464.2 (M+H)

Workup

  1. customThe reaction mixture was placed in a preheated oil bath at 140° C.
  2. additionThis addition
  3. customAfter removal of solvent
  4. customthe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-a6d37526899c4ac7adb33f31a8b2ea05
Source dataset
uspto-grants-2013_11
Patent number
US08592581B2

Reaction notes

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