Formaldehyde → Methyl 1,3-thiazole-4-carboxylate

To a solution of 2-[(S)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-(4-nitro-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester (53.9 mg, 0.1 mmol) in tetrahydrofuran (10 mL) was added sodium acetate (60 mg, 0.44 mmol), 37% w/w aqueous formaldehyde solution (0.033 mL, 0.44 mmol) and 10% palladium on carbon (30 mg) and the mixture shaken under an atmosphere of hydrogen at 50 psi pressure in a Parr apparatus for 72 hours. The reaction mixture was filtered through a pad of Celite® and washed through with additional tetrahydrofuran. The filtrate was concentrated in vacuo, the residue was dissolved in dichloromethane, washed with water, saturated aqueous sodium bicarbonate, dried with sodium sulfate and concentrated in vacuo to give the crude product as a yellow solid. Purification by reverse phase HPLC using a C18 stationary phase gradient eluted from 10% up to 90% acetonitrile in water gave 2-(S)-3-(4-dimethylamino-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-propionylamino}-thiazole-4-carboxylic acid methyl ester as a colorless solid (12 mg, 22%).

1. filtrationThe reaction mixture was filtered through a pad of Celite®
2. washwashed through with additional tetrahydrofuran
3. concentrationThe filtrate was concentrated in vacuo
4. dissolutionthe residue was dissolved in dichloromethane
5. washwashed with water, saturated aqueous sodium bicarbonate
6. dry with materialdried with sodium sulfate
7. concentrationconcentrated in vacuo
8. customto give the crude product as a yellow solid
9. customPurification by reverse phase HPLC
10. washeluted from 10% up to 90% acetonitrile in water

ORD record

ord-5e96646c3cd64def9d1f73300964f5b4

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07371869B2