Glutaric anhydride → 5-(5-Nitrothiazol-2-ylamino)-5-oxopentanoic acid

Glutaric anhydride (1.0 g, 8.8 mmol), TEA (1.35 ml, 9.6 mmol) and cat. DMAP were dissolved in CH2Cl2 (7 mL). 2-Amino-5-nitrothiazole (1.4 g, 9.64 mmol) was then added and the solution was held at ambient temperature. After 18 hours, the solution was diluted with EtOAc (50 mL) and extracted with 1M NaOH (3×30 mL). The combined aqueous layers were washed with EtOAc (20 mL) then acidified with 12M HCl and subsequently extracted with EtOAc (5×20 mL). The combined organics were washed with brine (2×20 mL), dried (MgSO4), filtered and concentrated to dryness to yield 5-(5-nitrothiazol-2-ylamino)-5-oxopentanoic acid (1.13 g, 54%) as an orange solid. 1H NMR (300 MHz, DMSO-d6) δ 12.59 (bs, 1H), 8.59 (s, 1H), 2.57 (t, J=7.4 Hz, 2H), 2.28 (t, J=7.3 Hz, 2H), 1.82 (quint., J=7.3 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 174.0, 172.8, 161.8, 142.8, 141.7, 34.1, 32.7, 19.6; HRMS (ESI) calcd for [C8H9N3O5S+H]+260.0336. found 260.0344. Method B with 5-(5-nitrothiazol-2-ylamino)-5-oxopentanoic acid (30 mg, 0.12 mmol) afforded the title compound VPC161276 (23 mg, 46%) as an orange solid. 1H NMR (300 MHz, DMSO-d6) δ 8.61 (s, 2H), 2.61 (t, J=7.2 Hz, 4H), 1.97 (quint., J=7.0 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 172.8, 162.0, 142.8, 141.5, 34.0, 19.3; HRMS (ESI) calcd for [C11H10N6O6S2+H]+387.0176. found 387.0185.

1. customwas held at ambient temperature
2. extractionextracted with 1M NaOH (3×30 mL)
3. washThe combined aqueous layers were washed with EtOAc (20 mL)
4. extractionsubsequently extracted with EtOAc (5×20 mL)
5. washThe combined organics were washed with brine (2×20 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated to dryness

ORD record

ord-950f386e609d4d43b13d0f41e2357a0f

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09333193B2