Diisopropylethylamine → Tert-butyl 2-(2-((1-(cyclohexylmethyl)piperidine-4-yl)(methyl)amino)-2-oxoethoxy)-4,6-dimethylpyrimidine-5-ylcarbamate

HRID 2280899Notes

Reaction equation

HRID 2280899 reaction equation
Br[CH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[CH3:18][C:19]1[C:24]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[C:23]([CH3:33])[N:22]=[C:21]([O:34][CH2:35][C:36]([N:38]([CH3:45])[CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)=[O:37])[N:20]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH:3]1([CH2:2][N:42]2[CH2:41][CH2:40][CH:39]([N:38]([CH3:45])[C:36](=[O:37])[CH2:35][O:34][C:21]3[N:20]=[C:19]([CH3:18])[C:24]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[C:23]([CH3:33])[N:22]=3)[CH2:44][CH2:43]2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 137636Cyclohexane, (bromomethyl)-HCID 516892Sodium BicarbonateHCID 59336171Tert-butyl 4,6-dimethyl-2-(2-(methyl(piperidine-4-yl)amino)-2-oxoethoxy)pyrimidine-5-ylcarbamate

Product 1

HCID 59336176Tert-butyl 2-(2-((1-(cyclohexylmethyl)piperidine-4-yl)(methyl)amino)-2-oxoethoxy)-4,6-dimethylpyrimidine-5-ylcarbamateYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Bromomethyl cyclohexane (25 μL) and diisopropylethylamine (63 μL) were added to a solution of Compound 31 (71 mg) in dimethylformamide (1 mL) and the mixture was stirred at 120° C. for 8 hours. Subsequently, a saturated aqueous sodium bicarbonate solution was added to the reaction mixture and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (hexane:ethyl acetate=1:1) to give 40 mg (46% yield) of the desired product.

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-539379b550bb40c3b5634c0e7d888882
Source dataset
uspto-grants-2015_09
Patent number
US09139559B2

Reaction notes

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