1-Methyl-4-piperidone → 1-Methyl-4-{5-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-piperidin-4-ol

HRID 1434946Notes

Reaction equation

Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1.[Li]CCCC.[CH3:29][N:30]1[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]1>C1COCC1>[CH3:29][N:30]1[CH2:35][CH2:34][C:33]([C:2]2[S:6][C:5]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]4[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]4)[N:8]=3)=[CH:4][CH:3]=2)([OH:36])[CH2:32][CH2:31]1

Participants

Conditions

Temperature: -78 °C

Procedure

[4-(5-Bromo-thiophen-2-yl)-pyrimidin-2-yl]-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine (Step C of Example 5, 198 mg, 0.5 mmol) was dissolved in THF (10 ml), cooled to −78° C. and treated with nBuLi (1.6M in hexane, 0.94 ml, 1.5 mmol) for 15 minutes. N-methyl-4-piperidone (231 μl, 2 mmol) in THF (0.2 ml) was added rapidly and the reaction mixture stirred for 15 minutes at −78° C., then 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 preparative HPLC to give the title compound as colorless crystals, which crystallized from ether. Yield: 40 mg (19%).

Workup

additionpoured on water
extractionextracted three times with EtOAc
dry with materialThe combined organic phases were dried over sodium sulfate
filtrationfiltered
customevaporated to dryness
custompurified via preparative HPLC

Sources & evidence

ORD record: ord-e6777f74ed3749478e71e018e2955b3f
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615562B2

Reaction notes

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