Isopropanol → HCID 178421670, compound

HRID 535757Notes

Reaction equation

HRID 535757 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:26]2([CH3:29])[CH2:28][CH2:27]2)[N:5](COCC[Si](C)(C)C)[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][C:16]#[N:17])[N:8]=1.CC(O)C.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.C([O-])(O)=O.[Na+]>O.N1C=CC=CC=1>[Br:1][C:2]1[N:3]=[C:4]([C:26]2([CH3:29])[CH2:27][CH2:28]2)[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][C:16]#[N:17])[N:8]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 516892Sodium BicarbonateHCID 67053596HCID 67053596, compound

Product 1

HCID 178421670HCID 178421670, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To a 200 mL round-bottom flask containing 3-(4-(4-bromo-2-(1-methylcyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (2.46 g, 5.2 mmol) were added 2-propanol (10 mL) and PPTS (1.94 g, 7.7 mmol). The reaction was heated to 90° C. in an oil bath for 3 hours, LCMS indicated 90% conversion. Additional pyridine (100 μL) and the reaction was maintained at 90° C. for another 5 hours. The reaction was allowed to cool to room temperature and to an yellow gum. Added water (100 mL), adjusted to pH 7 with saturated aqueous NaHCO3 solution, and extracted with EtOAc (2×100 mL). Combined EtOAc, washed with saturated NaHCO3 (1×100 mL), brine (1×100 mL), dried (Na2SO4), filtered, and concentrated to obtain tacky yellow solids. The residue was triturated in EtOAc-Et2O (1 mL, 10 mL) to furnish 3-(4-(4-bromo-2-(1-methylcyclopropyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propanenitrile (1.50 g, 4.10 mmol, 95% purity by LCMS) as off-white solids: LCMS (m/z) 347.0 (MH+), tR=0.59 minute; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J=6.3 Hz, 1H), 7.54 (d, J=6.3 Hz, 1H), 3.88 (t, J=6.3 Hz, 2H), 2.75 (t, J=6.5 Hz, 2H), 1.47 (s, 3H), 1.22 (m, 2H), 0.84 (m, 2H).

Workup

  1. temperatureto cool to room temperature and to an yellow gum
  2. extractionextracted with EtOAc (2×100 mL)
  3. washCombined EtOAc, washed with saturated NaHCO3 (1×100 mL), brine (1×100 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto obtain tacky yellow solids
  8. customThe residue was triturated in EtOAc-Et2O (1 mL, 10 mL)

Sources & evidence

ORD record
ord-fa7faa81b81e4596874e49518f9e40b3
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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