Triethylamine → 4-[4-(pyrimidin-2-ylmethoxy)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid adamantan-2-ylamide

HRID 1510031Notes

Reaction equation

HRID 1510031 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1.C(N(CC)CC)C.ClC(Cl)(O[C:36](=[O:42])OC(Cl)(Cl)Cl)Cl.Cl.[CH:45]12[CH2:54][CH:49]3[CH2:50][CH:51]([CH2:53][CH:47]([CH2:48]3)[CH:46]1[NH2:55])[CH2:52]2>ClCCl>[CH:45]12[CH2:54][CH:49]3[CH2:50][CH:51]([CH2:53][CH:47]([CH2:48]3)[CH:46]1[NH:55][C:36]([N:18]1[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:2]4[N:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[CH:14][CH:13]=3)[CH2:16][CH2:17]1)=[O:42])[CH2:52]2

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 253312-Aminoadamantane hydrochlorideHCID 94429Triphosgene2×HCID 668635751-[4-(Pyrimidin-2-ylmethoxy)phenyl]-1,2,3,4-tetrahydroquinoxaline

Product 1

HCID 441555444-[4-(pyrimidin-2-ylmethoxy)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid adamantan-2-ylamideYield 57.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.095 g of 1-[4-(pyrimidin-2-ylmethoxy)phenyl]-1,2,3,4-tetrahydroquinoxaline is placed in 3 ml of dichloromethane at 0° C. under nitrogen. 0.09 ml of triethylamine and 0.031 g of triphosgene are added. The mixture is stirred at ambient temperature for 2 h 30, 0.01 g of triphosgene is then added and stirring is maintained for 2 h. 0.12 ml of triethylamine and 0.062 g of adamantan-2-ylamine hydrochloride are then added. Stirring is maintained at ambient temperature for 1 h. After hydrolysis, the reaction medium is extracted with ethyl acetate until the aqueous phase has been completely extracted. The organic phases are combined, washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol in dichloromethane varying from 0% to 9/1. 0.03 g of 4-[4-(pyrimidin-2-ylmethoxy)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid adamantan-2-ylamide is obtained, which is triturated from a mixture of ethyl acetate and diisopropyl ether.

Workup

  1. additionis then added
  2. temperatureis maintained for 2 h
  3. stirringStirring
  4. customAfter hydrolysis
  5. extractionthe reaction medium is extracted with ethyl acetate until the aqueous phase
  6. extractionhas been completely extracted
  7. washwashed with a saturated aqueous sodium chloride solution
  8. dry with materialdried over magnesium sulphate
  9. concentrationconcentrated to dryness
  10. customThe crude product obtained
  11. customis chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-c82ee6475cd74ed78dc8af283587ed30
Source dataset
uspto-grants-2012_07
Patent number
US08211892B2

Reaction notes

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