Hydrochloric Acid → HCID 178502279, compound

HRID 538410Notes

Reaction equation

HRID 538410 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:33]([CH3:36])([CH3:35])[CH3:34])[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][C@@H:15]([NH:17][C:18](=[O:24])[O:19][C:20](C)(C)C)[CH3:16])[N:8]=1.Cl.C([O-])(O)=O.[Na+].ClC(OC)=O>CO.C1COCC1.O>[Br:1][C:2]1[N:3]=[C:4]([C:33]([CH3:34])([CH3:36])[CH3:35])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17][C:18](=[O:24])[O:19][CH3:20])[CH3:16])[N:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformate2×HCID 516892Sodium BicarbonateHCID 66595367HCID 66595367, compound

Product 1

HCID 178502279HCID 178502279, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a solution of (S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (2.66 g, 3.94 mmol, Example 7, Step 1) in MeOH (17 ml) was added aqueous concentrated HCl (1.97 ml, 23.65 mmol) and the resulting reaction was stirred at 60° C. for 1 h. The reaction was allowed to cool to rt and concentrated in vacuo to give 2.28 g of crude residue. This material was then suspended in 1:1 THF-water (100 mL) followed by the addition of NaHCO3 (1.66 g, 19.70 mmol). The mixture was cooled to 5° C. and methyl chloroformate (1.0 M in THF, 4.33 ml, 4.33 mmol) was added dropwise. After 50 min, an additional charge of methyl chloroformate (1.0 M in THF, 4.33 ml, 4.33 mmol) was added and the reaction maintained for 45 min at 0° C. The reaction was quenched with water (300 mL) and the resulting layers were separated. The aqueous phase was extracted with EtOAc (2×200 mL) and the combined organic portions were washed with brine (2×400 mL), dried (Na2SO4), and concentrated. The resulting residue was triturated with 1:4 EtOAc-hexanes (10 mL) and washed with ether to provide 958 mg of (S)-methyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate: LCMS (m/z): 411.0 (MH+), tR=0.65 min.

Workup

  1. customthe resulting reaction
  2. temperatureto cool to rt
  3. concentrationconcentrated in vacuo
  4. customto give 2.28 g of crude residue
  5. temperatureThe mixture was cooled to 5° C.
  6. waitAfter 50 min
  7. additionwas added
  8. temperaturethe reaction maintained for 45 min at 0° C
  9. customThe reaction was quenched with water (300 mL)
  10. customthe resulting layers were separated
  11. extractionThe aqueous phase was extracted with EtOAc (2×200 mL)
  12. washthe combined organic portions were washed with brine (2×400 mL)
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated
  15. customThe resulting residue was triturated with 1:4 EtOAc-hexanes (10 mL)
  16. washwashed with ether

Sources & evidence

ORD record
ord-f2333ea6f90b4b1d8d5c9cbbc79478b8
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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