تفاعل #171971

ord-bd5ebac325504f9093e51fc0747af9c9

معادلة التفاعل

Cc1[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c(C)c1C(=O)On1nnc2cccnc21
15b
Cc1[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c(C)c1C(=O)On1nnc2cccnc21
(Z)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylate
CCN(CC)CCN
N,N-diethylethane-1,2-diamine
CCN(CC)CCNC(=O)c1c(C)[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c1C
Sunitinib
المردود 88.0%

المذيبات

ظروف التفاعل

درجة الحرارة
25°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىthe completion of the reaction
  2. 2
    أخرىMost of the DMF was removed
  3. 3
    أخرىby rotary evaporating
  4. 4
    workup.STIRRINGstirred for another 1 hour
  5. 5
    ترشيحThe solid was collected by filtration
  6. 6
    غسيلwashed with MeCN
  7. 7
    أخرىdried under vacuum at 40° C. overnight

الإجراء التجريبي

15 (10 g, 33.3 mmol) was suspended in DMF (50 ml, 5 P.) and stirred for 5 minutes. DIPEA (9.0 mL, 54.5 mmol) was then added and the mixture was stirred for 10 minutes. HATU (13.95 g, 36.7 mmol) was added and the reaction mixture was stirred at 25° C. for completion. HPLC was applied to detect the completion of the reaction. Most of the DMF was removed by rotary evaporating and the residue was suspended in MeCN (100 mL, 10 P.) and stirred for another 1 hour. The solid was collected by filtration, washed with MeCN, and dried under vacuum at 40° C. overnight. The intermediate (Z)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylate (15b) (12 g, 86.5 percent yield) with 86.8% HPLC purity as a yellow powder was got. 1H NMR (300 MHz, DMSO-d6): δ 2.61 (s, 3H, H-31), 2.68 (s, 3H, H-16), 6.87 (m, 1H, H-2), 7.01 (m, 1H, H-6), 7.64 (m, 1H, H-10), 7.85 (m, 1H, H-3), 8.73 (dd, J=1.5, 1.2 Hz, 1H, H-28), 8.83 (dd, J=1.2, 1.5 Hz, 1H, H-27), 13.11 (s, 1H, NH). To a 15b (10.0 g, 23.9 mmol) DMF solution was added N,N-diethylethane-1,2-diamine (7; 3.33 g, 28.7 mmol), the reaction mixture was stirred at 25° C. for completion. HPLC was applied to detect the completion of the reaction. Most of the DMF was removed by rotary evaporating and the residue was suspended in MeCN (100 mL, 10 P.) and stirred for another 1 hour. The solid was collected by filtration, washed with MeCN, and dried under vacuum at 40° C. overnight to give Sunitinib (8.38 g, 88% yield) with 77.6% HPLC purity.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08846953B2uspto-grants-2014_09