Sodium Carbonate → 4-[4-(1-Tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine

HRID 1359449

Reaction equation

HRID 1359449 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[Cl:7][C:8]1[N:13]=[C:12](Cl)[C:11]([Cl:15])=[CH:10][N:9]=1.CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][C:27]([C:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)O1>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:36]([O:35][C:34]([NH:33][C:30]([C:27]1[CH:26]=[CH:25][C:24]([C:12]2[C:11]([Cl:15])=[CH:10][N:9]=[C:8]([Cl:7])[N:13]=2)=[CH:29][CH:28]=1)([CH3:32])[CH3:31])=[O:40])([CH3:37])([CH3:38])[CH3:39]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2372592,4,5-TrichloropyrimidineHCID 231344434-[2-(Boc-amino)-2-propyl]phenylboronic Acid Pinacol Ester

Product 1

HCID 181832304-[4-(1-Tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidineYield 81.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

2M aqueous Na2CO3 (4.7 ml, 9.4 mmol) was added to a solution of 2,4,5-trichloropyrimidine [Chesterfield, J.; McOmie, J. F. W.; Sayer, E. R.; J. Chem. Soc. (1955) 3478-3481] (1.18 g, 6.44 mmol), tert-butyl N-{1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]1-methylethyl}carbamate (1.55 g, 4.29 mmol) and tetrakis(triphenylphosphine)palladium (O) (150 mg, 0.13 mmol) in ethyleneglycol dimethylether (20 ml) under N2 and the mixture heated to reflux for 6 h. The reaction was diluted with H2O (30 ml) and extracted with ethyl acetate (3×50 ml), the combined ethyl acetate extracts were washed with brine (30 ml), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (SiO2, 15% ethyl acetate in hexane) to give 4-[4-(1-tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine as a white solid (1.34 g). δH (d6DMSO) 8.62 (1H, s), 7.90 (2H, d, J 8.6 Hz), 7.54 (2H, dt, J 8.7, 2.1 Hz), 5.02 (1H, bs), 1.65 (6H, s) and 1.37 (9H, s).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 6 h
  3. extractionextracted with ethyl acetate (3×50 ml)
  4. washthe combined ethyl acetate extracts were washed with brine (30 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (SiO2, 15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-de03458ef4724dff92ed81cde0fe65f9
Source dataset
uspto-grants-2003_07
Patent number
US06600037B1

Linked notes

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