Dimethyl Sulfoxide → Sunitinib

HRID 84790

Reaction equation

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]

Participants

Conditions

Temperature: 55 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-9f8d5ca1e48a46a9873f62413325a61e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846953B2

Linked notes

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