Potassium Carbonate → HCID 90402383, compound

HRID 2200708Notes

Reaction equation

HRID 2200708 reaction equation
[OH:1][CH:2]([CH3:29])[CH2:3][CH2:4][N:5]1[C:13](=[O:14])[C:12]2[NH:11][C:10]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=3)=[N:9][C:8]=2[N:7]([CH3:27])[C:6]1=[O:28].Cl.Cl[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][N:34]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[OH:1][CH:2]([CH3:29])[CH2:3][CH2:4][N:5]1[C:13](=[O:14])[C:12]2[N:11]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][N:34]=3)[C:10]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:25])([F:26])[F:24])[CH:17]=3)=[N:9][C:8]=2[N:7]([CH3:27])[C:6]1=[O:28]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 233137952-(Chloromethyl)-5-methylpyridine hydrochloride2×HCID 90403565HCID 90403565, compound2×

Product 1

HCID 90402383HCID 90402383, compoundYield 31.9%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 1-(3-hydroxybutyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)— dione (50 mg, 0.121 mmol, intermediate 57) in DMF (3 mL) was added 2-(chloromethyl)-5-methylpyridine hydrochloride (30 mg, 0.182 mmol, intermediate 50), followed by potassium carbonate (50 mg, 0.363 mmol) and TBAI (10 mg, 0.027 mmol). The reaction was stirred at 65° C. overnight. The reaction was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product, which was purified by preparative HPLC to give 1-(3-hydroxybutyl)-3-methyl-7-((5-methylpyridin-2-yl)methyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (20 mg, 31.9% yield) as white solid. 1H-NMR (CD3OD) δ 8.319(s,1H), 7.663-7.640(d,1H), 7.553-7.510(t,1H), 7.348-7.316(m,3H), 7.233-7.208(m,1H), 5.609(s, 2H), 4.112-4.004(m,2H), 3.763-3.731(m,1H), 3.457(s,3H), 2.339(s,3H), 1.758-1.698(m,2H), 1.197-1.182(d,2H). LCMS retention time 2.714 min; LCMS MH+ 520.

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-6808b26aed4646a582a35a568a2c6dda
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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