3-Aminopropionitrile → HCID 67053596, compound

HRID 1043733Notes

Reaction equation

HRID 1043733 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-98a99f90ae5a4885a93a1826ecea37e8
Source dataset
uspto-grants-2013_10
Patent number
US08563553B2

Reaction notes

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