4-Bromoanisole → HCID 18323822, compound

HRID 1251505Notes

Reaction equation

HRID 1251505 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])(C)(C)C.CCCCC.[Br:20][C:21]1[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=1[N:30]([CH2:46][CH3:47])[C:31]1[N:36]=[C:35]([C:37]([C:39]2[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=2)=[O:38])[CH:34]=[C:33]([CH3:45])[N:32]=1.[NH4+].[Cl-]>C1COCC1.C(OCC)(=O)C>[Br:20][C:21]1[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=1[N:30]([CH2:46][CH3:47])[C:31]1[N:36]=[C:35]([CH:37]([C:39]2[CH:40]=[N:41][CH:42]=[CH:43][C:44]=2[C:6]2[CH:7]=[CH:2][CH:3]=[CH:4][C:5]=2[O:8][CH3:9])[OH:38])[CH:34]=[C:33]([CH3:45])[N:32]=1

Participants

8

Reactant 5

HCID 77304-BromoanisoleHCID 8003PentaneHCID 25517Ammonium ChlorideHCID 18323702HCID 18323702, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 18323822HCID 18323822, compoundYield 31.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 4-bromoanisole (0.2 g, 1.1 mmol) in anhydrous THF (10 mL) was cooled with stirring to −78° C. under a nitrogen atmosphere. A solution of t-butyl lithium in pentane (1.7 M, 1.4 mL, 2.4 mmol) was added dropwise and the reaction mixture was stirred for 0.5 h. A solution of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(3-pyridyl-carbonyl)-6-methylpyrimidinamine (0.45 g, 1 mmol) in anhydrous THF (10 mL) was added dropwise and the reaction mixture was warmed gradually to ambient temperature over 18 h. The reaction mixture was poured onto a saturated NH4Cl solution and extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an oil. Column chromatography (ethyl acetate:hexanes::4:1) afforded the title product as a pale brown glass (170 mg, 31% yield, Rf0.2): mp 68-70° C.; NMR (CDCl3, 300 MHz): 8.6-8.4 (m, 2H), 7.7-7.5 (m, 1H), 7.5 (s, 1H), 7.25-7.05 (m, 6H), 6.95-6.75 (m, 2H), 6.25-6.2 (m, 1H), 5.85-5.7 (m, 1H), 4.25-4.05 (m, 1H), 3.8 (br s, 3H), 3.95-3.75 (m, 1H), 3.00-2.8. (m, 1H), 2.45-2.1 (br s, 3H), 1.35-1.15 (m, 9H); CI-HRMS: Calcd(C29H31BrN4O2): 547.1709 (M+H), Found: 547.1709.

Workup

  1. stirringthe reaction mixture was stirred for 0.5 h
  2. temperaturethe reaction mixture was warmed gradually to ambient temperature over 18 h
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil

Sources & evidence

ORD record
ord-0278c8909e644eef8d134fb4f63645d8
Source dataset
uspto-grants-2002_01
Patent number
US06342503B1

Reaction notes

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