N,N-Diethylethylenediamine → Sunitinib

HRID 84789

反応式

HRID 84789 の反応式
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:17][C:16]([CH3:18])=[C:15]([C:19](ON2C3=NC=CC=C3N=N2)=[O:20])[C:14]=1[CH3:31].[CH2:32]([N:34]([CH2:38][CH3:39])[CH2:35][CH2:36][NH2:37])[CH3:33]>CN(C=O)C>[CH3:33][CH2:32][N:34]([CH2:35][CH2:36][NH:37][C:19]([C:15]1[C:14]([CH3:31])=[C:13](/[CH:12]=[C:5]2/[C:4]3[CH:3]=[C:2]([F:1])[CH:10]=[CH:9][C:8]=3[NH:7][C:6]/2=[O:11])[NH:17][C:16]=1[CH3:18])=[O:20])[CH2:38][CH3:39]

参加物

4

反応物 2

HCID 60993N,N-DiethylethylenediamineHCID 136141940(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

生成物 1

HCID 5329102Sunitinib収率 88%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

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.

後処理

  1. customthe completion of the reaction
  2. customMost of the DMF was removed
  3. customby rotary evaporating
  4. stirringstirred for another 1 hour
  5. filtrationThe solid was collected by filtration
  6. washwashed with MeCN
  7. customdried under vacuum at 40° C. overnight

出典と根拠

ORDレコード
ord-bd5ebac325504f9093e51fc0747af9c9
出典データセット
uspto-grants-2014_09
特許番号
US08846953B2

関連ノート

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