1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178500663, compound

Temperature

100 °C

Di-2-pyridyl thionocarbonate (367 mg, 1.58 mmol) was added in one portion to a stirred solution of 4-aminopyrimidine (150 mg, 1.58 mmol) in DCM (3 mL) and the reaction mixture was heated at 100° C. for 20 minutes in the microwave and then cooled to room temperature. This solution was added to a suspension of methyl [trans-4-(4-{[hydrazino(oxo)acetyl]amino}-phenyl)cyclohexyl]acetate (Intermediate 43, 421 mg, 1.26 mmol) in DCM (5 mL) and the mixture stirred at room temperature for 5 minutes. DMF (8 mL) was added and the DCM was removed under reduced pressure. The solution was heated at 85° C. for 40 minutes in the microwave and then cooled to room temperature. EDCI (303 mg, 1.58 mmol) was added in one portion and the reaction mixture was heated at 85° C. for 60 minutes in the microwave. The reaction was quenched by the addition of H2O (200 mL) and EtOAc (250 mL) was added. The layers were separated and the aqueous layer was extracted with EtOAc (2×150 mL). The combined organic layer was washed with brine (100 mL), dried (MgSO4) and concentrated in vacuo to leave a dark brown gummy solid. MeOH (40 mL) was added and the mixture was heated to reflux for 2 minutes and then cooled to room temperature to leave a white suspension. The solid was filtered to give the title compound (110 mg, 20%) as a solid; 1H NMR δ 1.10-1.17 (2H, m), 1.43-1.47 (2H, m), 1.75-1.81 (5H, m), 2.24-2.26 (2H, d), 2.44 (1H, t), 3.61 (3H, s), 7.24 (2H, d), 7.69-7.73 (2H, m), 7.92 (1H, d), 8.69 (1H, d), 8.87 (1H, s), 11.02 (1H, s); MS m/e MH+ 437.

1. temperaturecooled to room temperature
2. customthe DCM was removed under reduced pressure
3. temperatureThe solution was heated at 85° C. for 40 minutes in the microwave
4. temperaturecooled to room temperature
5. temperaturethe reaction mixture was heated at 85° C. for 60 minutes in the microwave
6. customThe reaction was quenched by the addition of H2O (200 mL) and EtOAc (250 mL)
7. additionwas added
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with EtOAc (2×150 mL)
10. washThe combined organic layer was washed with brine (100 mL)
11. dry with materialdried (MgSO4)
12. concentrationconcentrated in vacuo
13. customto leave a dark brown gummy solid
14. temperaturethe mixture was heated
15. temperatureto reflux for 2 minutes
16. temperaturecooled to room temperature
17. customto leave a white suspension
18. filtrationThe solid was filtered

ORD record

ord-f5fbcec5c6804b66bbab9527f9761509

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07795283B2