N,N,N',N'-Tetramethylethylenediamine → HCID 59605333, compound

HRID 1946162Notes

Reaction equation

HRID 1946162 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1.CN(CCN(C)C)C.[Li]CCCC.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41](=[O:44])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>C1COCC1>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41]([C:7]2[N:8]([CH3:11])[C:9]3[C:5]([N:6]=2)=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=[C:2]([Cl:1])[N:10]=3)([OH:44])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 715006872-Chloro-9-methyl-6-(4-morpholinyl)-9H-purineHCID 178418339Butyllithium

Product 1

HCID 59605333HCID 59605333, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a mixture of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine (2.5 g, 9.86 mmol) and TMEDA (2.1 mL, 14.8 mmol) in THF (80 mL) at −78° C. was added n-BuLi (6 mL, 2.5 M in hexanes, 14.8 mmol). The resulting mixture was allowed to warm to −30° C. for 30 min then cooled back to −78° C. before the addition of a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (2.9 g, 14.8 mmol) in THF (20 mL). The reaction mixture was slowly warmed to r.t. and stirred for 16 h then quenched with H2O and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 10-75%) affording 4-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (3.2 g, 71%). LCMS (method H): RT 3.52 min [M+H]+ 453.3

Workup

  1. temperatureThe reaction mixture was slowly warmed to r.t.
  2. customthen quenched with H2O
  3. extractionextracted with EtOAc
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 10-75%)

Sources & evidence

ORD record
ord-926c604296ae44388e4ac0996fcb205a
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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