Hydrochloric Acid → HCID 86699278, compound

HRID 2278625Notes

Reaction equation

HRID 2278625 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.CN(C1C=CC=CN=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[N:26]1([C:32]2[N:33]=[C:34]([CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[NH:35][C:36](=[O:38])[CH:37]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl>C1(C)C=CC=CC=1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[CH:1]1([N:35]2[C:36](=[O:38])[CH:37]=[C:32]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:33]=[C:34]2[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 218852-DimethylaminopyridineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 2760897Cyclopropylboronic acidHCID 135905419Ethyl 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate

Product 1

HCID 86699278HCID 86699278, compoundYield 7.8%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

643 mg of cyclopropylboronic acid, 680 g of copper(II) acetate, 1.37 g of dimethylaminopyridine and, finally, 6.23 ml of a solution of sodium bis(trimethylsilyl)amide (0.6M in toluene) are added, using a dropping funnel, to a solution of 1 g of ethyl [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, prepared in step 1d of example 1d, in 12 ml of toluene. The reaction mixture is heated at 95° C. for 16 and then cooled to ambient temperature. After the addition of 20 ml of an aqueous 1N hydrochloric acid solution and extraction with dichloromethane (3×50 ml), the organic phases are combined and then dried over magnesium sulfate, filtered through sintered glass, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (98/02 then 95/05 V/V). 90 mg of ethyl (1-cyclopropyl-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate are obtained in the form of a yellow oil, used as it is in the next step.

Workup

  1. temperaturecooled to ambient temperature
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered through sintered glass
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by silica column chromatography, elution
  6. additionbeing carried out with a mixture of dichloromethane and methanol (98/02

Sources & evidence

ORD record
ord-2c5c48ff2a464baa8aa95141bf4bdc24
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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