Dimethyl Sulfoxide → Sunitinib

HRID 84790

반응식

HRID 84790 반응식
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]

참가 물질

5

반응물 3

HCID 679Dimethyl SulfoxideHCID 962Water2회HCID 6456015Sunitinib Malate

생성물 1

HCID 5329102Sunitinib수율 74%

시약·촉매·용매 1

HCID 7909Methyl Isobutyl Ketone용매

반응 조건

온도
55 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9f8d5ca1e48a46a9873f62413325a61e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846953B2

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