p-Toluenesulfonic acid → Dactolisib tosylate

HRID 2090181Notes

Reaction equation

[CH3:1][C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:24]3[C:23]4[CH:22]=[C:21]([C:25]5[CH:26]=[N:27][C:28]6[C:33]([CH:34]=5)=[CH:32][CH:31]=[CH:30][CH:29]=6)[CH:20]=[CH:19][C:18]=4[N:17]=[CH:16][C:15]=3[N:14]([CH3:35])[C:13]2=[O:36])=[CH:8][CH:7]=1)([CH3:5])[C:3]#[N:4].[C:37]1([CH3:47])[CH:42]=[CH:41][C:40]([S:43]([OH:46])(=[O:45])=[O:44])=[CH:39][CH:38]=1>C(O)=O.CC(C)=O>[S:43]([C:40]1[CH:41]=[CH:42][C:37]([CH3:47])=[CH:38][CH:39]=1)([OH:46])(=[O:45])=[O:44].[CH3:5][C:2]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[C:24]3[C:23]4[CH:22]=[C:21]([C:25]5[CH:26]=[N:27][C:28]6[C:33]([CH:34]=5)=[CH:32][CH:31]=[CH:30][CH:29]=6)[CH:20]=[CH:19][C:18]=4[N:17]=[CH:16][C:15]=3[N:14]([CH3:35])[C:13]2=[O:36])=[CH:10][CH:11]=1)([CH3:1])[C:3]#[N:4]

Participants

Conditions

Temperature: 0 °C

Procedure

2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile (compound of formula I) is dissolved in formic acid at 56° C. and the resulting solution is clear filtered. The filtrate is then concentrated and a solution of p-toluenesulfonic acid (1.05 eq) in acetone is added within 30 minutes. After 25% and 50% of the addition volume, the mixture is seeded to initiate crystallization. A further amount of acetone is added and the suspension is cooled down to 0° C. The crystallized product (form A of compound I monotosylate) is collected by centrifugation and dried at 60° C. under vacuum.

Workup

concentrationThe filtrate is then concentrated
customcrystallization
additionA further amount of acetone is added
customThe crystallized product (form A of compound I monotosylate) is collected by centrifugation
customdried at 60° C. under vacuum

Sources & evidence

ORD record: ord-0216fe0f667942c284661179815ef2ad
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436177B2

Reaction notes

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