反应详情

温度

25 °C

0.40 g (0.998 mmol) of tert-butyl 3-amino-5-(1-methyl-1-phenylethylcarbamoyl)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate dissolved in 10 ml of pyridine is placed in a 50 ml round-bottomed flask under argon. 0.25 g (0.996 mmol) of 4-(4-morpholinyl)benzoyl chloride dihydrochloride (prepared according to WO 95/04729) is then gradually added and the mixture is stirred for 15 hours at 25° C. The reaction medium is then concentrated to dryness under reduced pressure (40° C.) and the residue is taken up in 50 ml of dichloromethane and 50 ml of water, and basified with 0.1N sodium hydroxide solution. The emulsion obtained is resorbed by saturation with sodium chloride. After separation of the phases by settling, the organic phase is dried over magnesium sulfate and concentrated to dryness under reduced pressure. The residue is purified by flash chromatography (msilica=30 g; eluent: 99/1 dichloromethane/methanol). 0.19 g of tert-butyl 5-(1-methyl-1-phenylethylcarbamoyl)-3-(4-morpholin-4-ylbenzoylamino)-1H-pyrazolo[4,3-d]thiazole-1-carboxylate is thus obtained in the form of a yellow foam. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.61 (s, 9H); 1.70 (s, 6H); 3.29 (masked m, 4H); 3.75 (m, 4H); 7.03 (d, J=8.5 Hz, 2H); 7.20 (t, J=7.5 Hz, 1H); 7.30 (t, J=7.5 Hz, 2H); 7.40 (d, J=7.5 Hz, 2H); 7.97 (d, J=8.5 Hz, 2H); 8.69 (s, 1H); 11.1 (broad m, 1H). LC-MS-DAD-ELSD: 591(+)=(M+H)(+); 535(+)=591(+)-tBu+H.

1. customis placed in a 50 ml round-bottomed flask under argon
2. concentrationThe reaction medium is then concentrated to dryness under reduced pressure (40° C.)
3. customThe emulsion obtained
4. customAfter separation of the phases
5. dry with materialthe organic phase is dried over magnesium sulfate
6. concentrationconcentrated to dryness under reduced pressure
7. customThe residue is purified by flash chromatography (msilica=30 g; eluent: 99/1 dichloromethane/methanol)