3-Aminopropionitrile → HCID 67053596, compound

HRID 535756Notes

Reaction equation

HRID 535756 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[Br:7][C:8]1[N:9]=[C:10]([C:28]2([CH3:31])[CH2:30][CH2:29]2)[N:11]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:12]=1[C:13]1[CH:18]=[CH:17][N:16]=[C:15](Cl)[N:14]=1.CCN(C(C)C)C(C)C.[NH2:41][CH2:42][CH2:43][C:44]#[N:45]>CN1C(=O)CCC1.CCOC(C)=O>[Br:7][C:8]1[N:9]=[C:10]([C:28]2([CH3:31])[CH2:30][CH2:29]2)[N:11]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:12]=1[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:45][CH2:44][CH2:43][C:42]#[N:41])[N:14]=1

Participants

7

Reactant 4

HCID 16473-AminopropionitrileHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 86651411HCID 86651411, compound

Product 1

HCID 67053596HCID 67053596, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

Solid Na2CO3 (1.11 g, 10.5 mmol) was added to a solution of 4-(4-bromo-2-(1-methylcyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (I-3a, step 4, 2.33 g, 5.2 mmol), DIEA (1.8 mL, 10.5 mmol), and 3-aminopropionitrile (1.2 mL, 15.7 mmol) in NMP (3 mL) and the resulting reaction mixture was heated to 90° C. After 5 hours, LCMS indicated complete reaction and the reaction was allowed to cool to room temperature. EtOAc (75 mL) was added the organic phase was washed with water (100 mL), dilute aqueous NaHCO3 solution (100 mL), brine (150 mL), dried (Na2SO4), and concentrated. Purification of the resulting residue by flash chromatography (SiO2, 0-50% EtOAc in heptane) provided 3-(4-(4-bromo-2-(1-methylcyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (2.47 g, 5.2 mmol, 99% yield) as a foamy off-white solid: LCMS (m/z) 477.1 (MH+), tR=0.98 minute.

Workup

  1. customthe resulting reaction mixture
  2. customreaction
  3. temperatureto cool to room temperature
  4. washwas washed with water (100 mL), dilute aqueous NaHCO3 solution (100 mL), brine (150 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the resulting residue by flash chromatography (SiO2, 0-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-339a80b0ab994256a2a5af78095bc0d0
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

Loading…