Triethylamine → {4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-4-oxo-butyl}-methyl-carbamic acid tert-butyl ester

HRID 219700

Reaction equation

HRID 219700 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:15])[CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.OC1C2N=NNC=2C=CC=1.[C:33]([C:37]1[N:42]=[C:41]([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH:40]=[C:39]([CH:49]2[CH2:52][CH2:51][CH2:50]2)[N:38]=1)([CH3:36])([CH3:35])[CH3:34].Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][CH2:11][C:12]([N:46]1[CH2:47][CH2:48][N:43]([C:41]2[CH:40]=[C:39]([CH:49]3[CH2:52][CH2:51][CH2:50]3)[N:38]=[C:37]([C:33]([CH3:36])([CH3:35])[CH3:34])[N:42]=2)[CH2:44][CH2:45]1)=[O:14])[CH3:15])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 106563904-{[(Tert-butoxy)carbonyl](methyl)amino}butanoic acidHCID 666733902-tert-Butyl-4-cyclobutyl-6-(piperazin-1-yl)pyrimidineHCID 178418300HCID 178418300, compound

Product 1

HCID 69026620{4-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-4-oxo-butyl}-methyl-carbamic acid tert-butyl esterYield 100.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6 g of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (27.6 mmol) and 5.53 g of triethylamine (54.6 mmol) were dissolved in 100 ml of dimethylformamide. 4.1 g of hydroxybenzotriazole (HOBt, 30.35 mmol), 7.6 g of 2-tert-butyl-4-(piperazin-1-yl)-6-cyclobutyl-pyrimidine (27.7 mmol), and 5.8 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodimide hydrochloride (EDCl, 30.26 mmol) were added at room temperature, and the reaction mixture was stirred for 16 h. The reaction mixture was partitioned between water and ethyl acetate, the organic phase dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using dichloromethane. Fractions containing the product were combined and the solvent evaporated to yield 13.1 g of the title compound.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. dry with materialthe organic phase dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe crude product was purified by chromatography on silica gel
  6. additionFractions containing the product
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-a2f5827f31c741f7a8a46aeb4a6b920a
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Linked notes

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