Tetrahydrofuran → HCID 66600098, compound

HRID 1811876Notes

Reaction equation

HRID 1811876 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.F[C:12]1[N:17]=[CH:16][C:15]([CH2:18][N:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[CH:14][C:13]=1[C:32]1[N:40]=[C:39]([CH3:41])[N:38]=[C:37]2[C:33]=1[N:34]=[CH:35][N:36]2[CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][O:43]1.[NH2:48][C:49]1[CH:50]=[N:51][C:52]([O:55][CH3:56])=[CH:53][CH:54]=1.O1CCCC1>>[CH3:56][O:55][C:52]1[N:51]=[CH:50][C:49]([NH:48][C:12]2[N:17]=[CH:16][C:15]([CH2:18][N:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:14][C:13]=2[C:32]2[N:40]=[C:39]([CH3:41])[N:38]=[C:37]3[C:33]=2[N:34]=[CH:35][N:36]3[CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][O:43]2)=[CH:54][CH:53]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 59548429tert-butyl 4-((6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate

Product 1

HCID 66600098HCID 66600098, compoundYield 75%

Procedure

LiHMDS (1.0 M in THF, 3.75 mL, 3.75 mmol) was slowly added to a stirred mixture of tert-butyl 4-((6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate (0.6397 g, 1.250 mmol) and 3-amino-6-methoxypyridine (Aldrich, St. Louis, Mo.; 186 mg, 1.50 mmol) in tetrahydrofuran (10 mL, 1.250 mmol) at 0° C. and the mixture was stirred at the same temperature for 1 h before being quenched with NH4Cl(aq) (10 mL) and water (10 mL). The separated aqueous layer was extracted with EtOAc (3×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by flash column chromatograph (hexanes to 50% ethyl acetate/hexanes) to give tert-butyl 4-((6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate (0.577 g, 0.937 mmol, 74.9% yield) as a yellow foam. LCMS (API-ES) m/z 616 (M+H)+.

Workup

  1. custombefore being quenched with NH4Cl(aq) (10 mL) and water (10 mL)
  2. extractionThe separated aqueous layer was extracted with EtOAc (3×15 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. custompurified by flash column chromatograph (hexanes to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-69d75f7d35204d6d8575fcccf0307e86
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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