Ammonia → HCID 57433125, compound

HRID 2047676Notes

Reaction equation

HRID 2047676 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][CH:33]([OH:38])[C:34]([F:37])([F:36])[F:35].N.FC(F)(F)C1CO1>CCCCO.CS(C)=O>[F:35][C:34]([F:37])([F:36])[CH:33]([OH:38])[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

Participants

7

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 4189653-Amino-1,1,1-trifluoropropan-2-olHCID 5207692-(Trifluoromethyl)oxiraneHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amine

Product 1

HCID 57433125HCID 57433125, compoundYield 15%

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-trifluoropropan-2-ol (1 g, 7.8 mmol) [prepared from the reaction of ammonia with 2-(trifluoromethyl)oxirane]. 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 oil (62 mg, 15%). δH (CDCl3, 500 MHz) 1.53 (6 H, d, J 7.5, CH[CH3]2), 3.64-3.6 (1 H, m, NHCHHCOH[CF3][CH3), 3.76-3.73 (1 H, m, NHCHHCOH[CF3][CH3), 4.18-4.16 (1 H, m, CHMe2), 4.62-4.56 (1 H, m, CHOHCF3), 4.72 (3 H, s, br, NHCH2Ar and NHCH2Ar), 7.22-7.2 (1 H, m, ArH), 7.52 (1 H, s, ArH), 7.66 (1 H, d, J 10, ArH), 8.47 (1 H, d, J 5, ArH), 8.58 (1 H, s, ArH); δC (CDCl3, 500 MHz) 159.77 (C), 154.68 (C), 149.04 (CH), 148.45 (CH), 135.44 (CH), 135.03 (CH), 134.44 (C), 125.91 (C), 123.49 (CH), 114.78 (C), 71.57 (CH), 46.76 (CH), 42.94 (CH2), 32.2 (CH2), 22.47 (2×CH3) 19FNMR δ −78.48; m/z 396.2 (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-790ac721d17f49dab818172f3d017d33
Source dataset
uspto-grants-2013_11
Patent number
US08592581B2

Reaction notes

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