1-Methyl-4-piperidone → 1-Methyl-4-{4-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-phenyl}-piperidin-4-ol

HRID 1434986Notes

Reaction equation

HRID 1434986 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]3[CH2:20][C:19]([CH3:22])([CH3:21])[NH:18][C:17]([CH3:24])([CH3:23])[CH2:16]3)[N:9]=2)=[CH:4][CH:3]=1.[Li]CCCC.[CH3:30][N:31]1[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]1>C1COCC1.CCC(C)C.C1COCC1>[CH3:30][N:31]1[CH2:36][CH2:35][C:34]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([NH:14][CH:15]4[CH2:16][C:17]([CH3:24])([CH3:23])[NH:18][C:19]([CH3:22])([CH3:21])[CH2:20]4)[N:9]=3)=[CH:6][CH:7]=2)([OH:37])[CH2:33][CH2:32]1

Participants

6

Reactant 3

HCID 740491-Methyl-4-piperidoneHCID 57936126[4-(4-Bromophenyl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amineHCID 178418339Butyllithium

Product 1

HCID 579362251-Methyl-4-{4-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-phenyl}-piperidin-4-ol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 86610959THF isopentaneSolvent

Procedure

[4-(4-Bromophenyl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine (116 mg; 0.3 mmol) in THF/isopentane (3 ml/0.6 ml) was cooled to −100° C. nBuLi (1.6M in hexane, 0.56 ml; 0.9 mmol) was added within 5 minutes and the reaction mixture stirred for 15 minutes at this temperature. N-methyl-4-piperidone (71 μl, 0.6 mmol) was added in THF (71 μl), the reaction mixture stirred for 10 minutes at −100° C., poured on water and extracted three times with EtOAc. The combined organic phases were dried over sodium sulfate, filtered, evaporated to dryness and purified via chromatography on silicagel (EtOAc/MeOH/ammonia:90/9/1 to 80/18/2) to give the title compound as a white solid. Yield: 25 mg (17%).

Workup

  1. additionwas added within 5 minutes
  2. stirringthe reaction mixture stirred for 10 minutes at −100° C.
  3. additionpoured on water
  4. extractionextracted three times with EtOAc
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. custompurified via chromatography on silicagel (EtOAc/MeOH/ammonia:90/9/1 to 80/18/2)

Sources & evidence

ORD record
ord-e853bfed3e8c4a1885d0b81aff153309
Source dataset
uspto-grants-2009_11
Patent number
US07615562B2

Reaction notes

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