Dimethyl Sulfoxide → Sunitinib

HRID 84790

反応式

HRID 84790 の反応式
CS(C)=O.O.[CH3:6][CH2:7][N:8]([CH2:11][CH2:12][NH:13][C:14]([C:16]1[C:17]([CH3:34])=[C:18](/[CH:22]=[C:23]2/[C:24]3[CH:25]=[C:26]([F:33])[CH:27]=[CH:28][C:29]=3[NH:30][C:31]/2=[O:32])[NH:19][C:20]=1[CH3:21])=[O:15])[CH2:9][CH3:10].C(C(O)=O)[C@H](O)C(O)=O>CC(CC(C)=O)C>[CH3:6][CH2:7][N:8]([CH2:11][CH2:12][NH:13][C:14]([C:16]1[C:17]([CH3:34])=[C:18](/[CH:22]=[C:23]2/[C:24]3[CH:25]=[C:26]([F:33])[CH:27]=[CH:28][C:29]=3[NH:30][C:31]/2=[O:32])[NH:19][C:20]=1[CH3:21])=[O:15])[CH2:9][CH3:10]

参加物

5

反応物 3

HCID 679Dimethyl SulfoxideHCID 962Water2 回HCID 6456015Sunitinib Malate

生成物 1

HCID 5329102Sunitinib収率 74%

試薬・触媒・溶媒 1

HCID 7909Methyl Isobutyl Ketone溶媒

反応条件

温度
55 °C

実験手順

A mixture of DMSO (22.5 mL, 4.50 P, water content by Karl Fischer analysis 303 ppm) and water (0.1 mL, 0.02 P, 0.6 eq.) was pre-heated to 55° C. and Sunitinib malate (5.0 g, 99.48% purity by HPLC analysis, 1.0 eq.) was charged into the solvent and stirred for 25 min at 55° C. Then a mixture of MIBK (60 mL, 12 P, water content by Karl Fischer analysis 76 ppm) and water (0.1 mL, 0.02 P, 0.6 eq.) was charge at 55° C. The mixture was cooled to 20° C. and further stirred for about 30 h. The mixture was filtered and the cake was washed with MIBK (20 mL, 4.0 P, water content by Karl Fischer analysis 76 ppm), then was dried under vacuum at 40° C. overnight to give a sunitinib new malate salt form (3.70 g, 74.0% yield) as an orange to red powder with about 99.58% purity by HPLC analysis. m.p. 213° C.˜216° C.

後処理

  1. additionwas charge at 55° C
  2. temperatureThe mixture was cooled to 20° C.
  3. stirringfurther stirred for about 30 h
  4. filtrationThe mixture was filtered
  5. washthe cake was washed with MIBK (20 mL, 4.0 P, water content by Karl Fischer analysis 76 ppm)
  6. customwas dried under vacuum at 40° C. overnight

出典と根拠

ORDレコード
ord-9f8d5ca1e48a46a9873f62413325a61e
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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