Diisopropylethylamine → Paliperidone

HRID 448537Notes

Reaction equation

Cl[CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH2:11][CH2:12][CH2:13][CH:14]([OH:15])[C:7]2=[N:6][C:5]=1[CH3:16].C(N(C(C)C)CC)(C)C.[F:26][C:27]1[CH:41]=[CH:40][C:30]2[C:31]([CH:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)=[N:32][O:33][C:29]=2[CH:28]=1>CO>[CH3:16][C:5]1[N:6]=[C:7]2[N:8]([CH2:11][CH2:12][CH2:13][CH:14]2[OH:15])[C:9](=[O:10])[C:4]=1[CH2:3][CH2:2][N:37]1[CH2:36][CH2:35][CH:34]([C:31]2[C:30]3[CH:40]=[CH:41][C:27]([F:26])=[CH:28][C:29]=3[O:33][N:32]=2)[CH2:39][CH2:38]1

Participants

Conditions

Temperature: 62.5 °C

Procedure

3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (formula-7) (5.2 grams) and diisopropyl ethyl amine (12.56 grams) was added to 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (formula-8) (5.0 grams) in methanol (75 ml) taken in autoclave and then heated to 60-65° C., 0.8 Kg pressure was applied and stirred for 16 hours. The reaction mixture cooled and then distilled under reduced pressure. Isopropyl alcohol was added to the obtained residue and stirred for 15 minutes and then distilled off under reduced pressure to get the title compound. Added methanol and heated the reaction mixture to reflux temperature and stirred for 2.0 hrs at same temperature. Cooled the reaction mixture to 20° C. and stirred for 90 minutes at the same temperature. Filtered the solid precipitated. Washed the solid with chilled methanol and dried the compound.

Workup

temperatureThe reaction mixture cooled
distillationdistilled under reduced pressure
additionIsopropyl alcohol was added to the obtained residue
stirringstirred for 15 minutes
distillationdistilled off under reduced pressure

Sources & evidence

ORD record: ord-0416c7d83c574c8da6b1a846bf4d9b9d
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481729B2

Reaction notes

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