Sodium Carbonate → 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)-2-methylpropanenitrile

HRID 1043722Notes

Reaction equation

HRID 1043722 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:22]2[CH2:24][CH2:23]2)[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9](Cl)[N:8]=1.CCN(C(C)C)C(C)C.[NH2:34][CH2:35][CH:36]([CH3:39])[C:37]#[N:38].C([O-])([O-])=O.[Na+].[Na+]>CN1C(=O)CCC1>[Br:1][C:2]1[N:3]=[C:4]([CH:22]2[CH2:24][CH2:23]2)[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:38][CH2:37][CH:36]([CH3:39])[C:35]#[N:34])[N:8]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 789473-Amino-2-methylpropanenitrileHCID 81531DiisopropylethylamineHCID 866514084-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

Product 1

HCID 698104673-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)-2-methylpropanenitrileYield 100%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (2.5 g, 5.8 mmol), DIEA (2.0 mL, 11.6 mmol), and 3-amino-2-methylpropanenitrile (1.49 g, 17.7 mmol) in NMP (10 mL) was treated with Na2CO3 (1.23 g, 11.6 mmol) and the resulting reaction mixture heated at 90° C. overnight. The reaction was allowed to cool to room temperature and was partitioned between EtOAc (75 mL) and water (100 mL). The layers were separated and the organic portion was washed with saturated aqueous NaHCO3 solution (100 mL), brine (150 mL), dried (Na2SO4) and concentrated to a brown residue. Purification by flash chromatography (0-50% EtOAc-heptane) afforded 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)-2-methylpropanenitrile (2.79 g, 5.8 mmol) as a white solid: LCMS (m/z) 477.1 (MH+), tR=0.98 minute.

Workup

  1. customthe resulting reaction mixture
  2. temperatureto cool to room temperature
  3. customwas partitioned between EtOAc (75 mL) and water (100 mL)
  4. customThe layers were separated
  5. washthe organic portion was washed with saturated aqueous NaHCO3 solution (100 mL), brine (150 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to a brown residue
  8. customPurification by flash chromatography (0-50% EtOAc-heptane)

Sources & evidence

ORD record
ord-b80b2ff4cc844196a7447ca400444b13
Source dataset
uspto-grants-2013_10
Patent number
US08563553B2

Reaction notes

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