Ammonia → HCID 57456922, compound

To a solution of triphosgene (68 mg, 0.224 mmol) in dry dichloromethane (2 mL) was added dropwise a mixture of 1-(2-amino-4,5-dimethylthiophen-3-yl)propan-1-one (Example 51b) (111 mg, 0.605 mmol) and DIEA (0.24 mL, 1.344 mmol) in dry dichloromethane (3.5 mL) over a period of 20 minutes. After the reaction mixture was stirred for 5 minutes, a mixture of ammonia (7 M in MeOH, 0.086 mL, 0.605 mmol) and DIEA (0.24 mL, 1.344 mmol) in dry dichloromethane (2 mL) was added in one portion. The reaction mixture was then stirred at room temperature for 1 h under nitrogen. The reaction mixture was concentrated to dryness. The residue was dissolved in EtOAc (50 mL) and then washed with 10% NaHSO4, 5% NaHCO3, and brine. The organic layer was dried over MgSO4, filtered and concentrated. The yellow residue was purified by chromatography on silica gel (Gradient 0-50% EtOAc in Hexanes) to give the title compound (15.4 mg, 30%). 1H NMR (400 MHz, CDCl3) δ1.18 (t, 3H, J=7.2 Hz), 2.25 (s, 3H), 2.30 (s, 3H), 2.87 (q, 2H, J=7.2 Hz), 4.77 (s, 2H), 11.99 (s, 1H). MS 227 (MH+).

1. additionwas added in one portion
2. stirringThe reaction mixture was then stirred at room temperature for 1 h under nitrogen
3. concentrationThe reaction mixture was concentrated to dryness
4. dissolutionThe residue was dissolved in EtOAc (50 mL)
5. washwashed with 10% NaHSO4, 5% NaHCO3, and brine
6. dry with materialThe organic layer was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe yellow residue was purified by chromatography on silica gel (Gradient 0-50% EtOAc in Hexanes)

ORD record

ord-a38c687ba48f4ceb87e9beb0bf625fed

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541421B2