Dimethylbarbituric acid → 4-(2-{4-[3-(tert-Butylamino-methyl)-phenyl]-pyrimidin-2-ylamino}-ethyl)-phenol

HRID 2386513Notes

Reaction equation

HRID 2386513 reaction equation
C(OC(=O)[N:6]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[N:15]=2)[CH:9]=1)C=C.C(N(C(C)C)CC)(C)C.CN1C(=O)CC(=O)N(C)C1=O>C(Cl)Cl.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:30]([NH:6][CH2:7][C:8]1[CH:9]=[C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][CH2:22][C:23]3[CH:24]=[CH:25][C:26]([OH:29])=[CH:27][CH:28]=3)[N:15]=2)[CH:11]=[CH:12][CH:13]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 3

HCID 69860Dimethylbarbituric acidHCID 81531DiisopropylethylamineHCID 67045134tert-Butyl-(3-{2-[2-(4-hydroxy-phenyl)-ethylamino]-pyrimidin-4-yl}benzyl)-carbamic acid allyl ester2×

Product 1

HCID 586034084-(2-{4-[3-(tert-Butylamino-methyl)-phenyl]-pyrimidin-2-ylamino}-ethyl)-phenolYield 78%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl-(3-{2-[2-(4-hydroxy-phenyl)-ethylamino]-pyrimidin-4-yl}benzyl)-carbamic acid allyl ester (intermediate 118, 176 mg) was dissolved in methylene chloride (5 mL), followed by addition of diisopropylethylamine (0.11 mL), 1,3-dimethylbarbituric acid (78 mg) then Pd(PPh3)4 (50 mg). The mixture was stirred at room temperature overnight. The mixture was washed with saturated NaHCO3, brine, dried over Na2SO4, filtered and chromatographed on silica gel with methylene chloride:methanol (95:5) to afford 112 mg of product in 78% yield. LC-MS showed the product had the expected M+H+ of 377. 1H NMR (Varian 300 MHz, CD3OD, shifts relative to the solvent peak at 3.31 ppm) δ 8.3 (d, 1H) 8.1 (s, 1H) 8.0 (d, 1H) 7.5 (m, 2H) 7.1 (m, 3H) 6.7 (m, 2H) 3.8 (s, 2H) 3.6 (m, 2H) 2.8 (m, 2H) 1.2 (s, 9H).

Workup

  1. washThe mixture was washed with saturated NaHCO3, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customchromatographed on silica gel with methylene chloride:methanol (95:5)

Sources & evidence

ORD record
ord-571f48e27eac4c4b94af97da5160b171
Source dataset
uspto-grants-2012_09
Patent number
US08268822B2

Reaction notes

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