Hydrochloric Acid → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-imidazolyl)carbonyl-6-methylpyrimidinamine

HRID 1251501Notes

Reaction equation

HRID 1251501 reaction equation
CN(C[N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)C.C([Li])CCC.[Br:15][C:16]1[CH:21]=[C:20]([CH:22]([CH3:24])[CH3:23])[CH:19]=[CH:18][C:17]=1[N:25]([C:28]1[N:33]=[C:32]([C:34](OC)=[O:35])[CH:31]=[C:30]([CH3:38])[N:29]=1)[CH2:26][CH3:27].Cl.[OH-].[Na+]>C(OCC)C.CO.C(Cl)(Cl)Cl>[Br:15][C:16]1[CH:21]=[C:20]([CH:22]([CH3:23])[CH3:24])[CH:19]=[CH:18][C:17]=1[N:25]([CH2:26][CH3:27])[C:28]1[N:33]=[C:32]([C:34]([C:6]2[NH:5][CH:9]=[CH:8][N:7]=2)=[O:35])[CH:31]=[C:30]([CH3:38])[N:29]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 38320731-(1H-Imidazol-1-yl)-N,N-dimethylmethanamineHCID 183237072-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-carbomethoxy-6-methyl-pyrimidineHCID 178418339Butyllithium

Product 1

HCID 18323725N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-imidazolyl)carbonyl-6-methylpyrimidinamineYield 42%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6212ChloroformSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(dimethylaminomethyl)imidazole (0.63 g, 5 mmol) in anhydrous diethyl ether (50 mL) at −78° C. under a nitrogen atmosphere was added a solution of n-butyl lithium in hexanes (2.4 M, 2.1 mL, 5 mmol) dropwise and the pale yellow suspension was stirred at −78° C. for 1 h. Methyl 2-(N-(2-bromo-4-(1-methylethyl)-phenyl)-N-ethylamino)-6-methyl-4-pyrimidinecarboxylate (Example 18) (1.47 g, 5 mmol) was added in one portion and the reaction mixture was warmed to room temperature over 23 h. A 1N HCl solution was added until pH=1 (test paper) and the reaction mixture was stirred for 4 h. A 3N NaOH solution was added until the solution became basic (pH=10; test paper). Three extractions with ethyl acetate, drying the combined organic layers over MgSO4, filtration and concentration in vacuo gave a brown oily solid. Column chromatography (chloroform:methanol::9:1) afforded the title product, a yellow glass (900 mg, 42% yield, Rf 0.43): mp 75-76° C.; NMR (CDCl3, 300 MHz): 12.2-12.1 (m, 1H), 7.7 (d, 1H, J=1), 7.45-7.35 (m, 2H), 7.3-7.2 (m, 2H), 6.55 (br s, 1H), 4.3 (sextet, 1H, J=7), 3.8 (sextet, 1H, J=7), 3.05 (septet, 1H, J=7), 2.65 (br s, 3H), 1.4 (d, 6H, J=7), 1.3 (t, 3H, J=7); CI-HRMS: Calcd: 428.1086 (M+H), Found: 428.1089; Anal (C20H24BrN5O) C, 56.08; H, 5.18; N, 16.35; Br, 18.66; Found: C, 56.20; H, 5.10; N, 15.88; Br, 18.73.

Workup

  1. temperaturethe reaction mixture was warmed to room temperature over 23 h
  2. stirringthe reaction mixture was stirred for 4 h
  3. extractionThree extractions with ethyl acetate
  4. customdrying the combined organic layers
  5. filtrationover MgSO4, filtration and concentration in vacuo
  6. customgave a brown oily solid

Sources & evidence

ORD record
ord-8dfaf5d627274507a07895158f234986
Source dataset
uspto-grants-2002_01
Patent number
US06342503B1

Reaction notes

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