تفاعل #10406

معادلة التفاعل

{7-[(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-benzylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}carbamic acid tert-butyl ester

{7-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-5-benzylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}carbamic acid tert-butyl ester

→

{5-amino-7-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}-carbamic acid tert-butyl ester

المردود 76.0%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىis hydrogenated at room temperature
2. 2
   ترشيحThe mixture is filtered through Celite
3. 3
   غسيلthe solid is washed with chloroform
4. 4
   تركيزthe combined filtrates concentrated under vacuum
5. 5
   أخرىPurification by column chromatography (2:3 ethyl acetate/hexanes)

الإجراء التجريبي

{7-[(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-benzylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 10 (0.435 g, 0.676 mmol) in tetrahydrofuran (20 mL) is hydrogenated at room temperature and atmospheric pressure over 20% palladium hydroxide on carbon (0.114 g) for 27 hours. The mixture is filtered through Celite, the solid is washed with chloroform, and the combined filtrates concentrated under vacuum. Purification by column chromatography (2:3 ethyl acetate/hexanes) gives {5-amino-7-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}-carbamic acid tert-butyl ester as a solid (0.284 g). 1H NMR (CDCl3): δ 6.61 (bs, 1H), 5.94 (bs, 2H), 4.82–4.69 (bd, 1H), 4.40–4.21 (m, 1H), 4.00–3.59 (m, 3H), 3.55–3.41 (m, 1H), 3.35–3.21 (m, 1H), 2.32–2.08 (m, 1H), 2.01–1.80 (m, 1H), 1.50 (s, 9H), 1.46 (s, 9H), 1.17–1.01 (m, 2H), 0.77–0.63 (m, 2H).

المصدر