3-(1-Piperazinyl)-1,2-benzisothiazole → Ziprasidone

HRID 1925223Notes

Reaction equation

HRID 1925223 reaction equation
Cl[CH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[Cl:13])[NH:9][C:8](=[O:14])[CH2:7]2.[S:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[N:16]1>O>[CH:22]1[CH:21]=[CH:20][C:19]2[S:15][N:16]=[C:17]([N:24]3[CH2:25][CH2:26][N:27]([CH2:2][CH2:3][C:4]4[CH:5]=[C:6]5[CH2:7][C:8](=[O:14])[NH:9][C:10]5=[CH:11][C:12]=4[Cl:13])[CH2:28][CH2:29]3)[C:18]=2[CH:23]=1

Participants

4

Reactant 2

HCID 27721443-(1-Piperazinyl)-1,2-benzisothiazoleHCID 106094745-(2-Chloroethyl)-6-chlorooxindole

Product 1

HCID 60854Ziprasidone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
99 °C

Procedure

To de-ionized water (2.0 Lit), was added 5-(2-chloroethyl)-6-chloro-oxindole (100 g) and 1-(1,2-benzisothiazol-3-yl)piperazine (210 g) at 30-35° C. The mixture was slowly heated under stirring to 98-100° C. over 60-80 minutes. The resultant mass was stirred for 10-15 hours at 98-100° C. After completion of reaction as monitored by HPLC, the suspended solid material was filtered at 98-100° C. The wet cake so obtained was suspended in de-ionized water (2.0 Lit) and heated to 90-95° C. and maintained at this temperature for 30 minutes. The solid suspension was filtered at 90-95° C. The wet cake was further added to isopropyl alcohol (1.5 Lit) and stirred for 2 hours at 30-35° C. The solids were filtered and washed with isopropyl alcohol (500 ml) and dried under vacuum at 50-55° C. for 7-8 hours till moisture content was not more than 1.0% w/w.

Workup

  1. temperatureThe mixture was slowly heated
  2. stirringThe resultant mass was stirred for 10-15 hours at 98-100° C
  3. customAfter completion of reaction
  4. filtrationthe suspended solid material was filtered at 98-100° C
  5. customThe wet cake so obtained
  6. temperatureheated to 90-95° C.
  7. temperaturemaintained at this temperature for 30 minutes
  8. filtrationThe solid suspension was filtered at 90-95° C
  9. additionThe wet cake was further added to isopropyl alcohol (1.5 Lit)
  10. stirringstirred for 2 hours at 30-35° C
  11. filtrationThe solids were filtered
  12. washwashed with isopropyl alcohol (500 ml)
  13. customdried under vacuum at 50-55° C. for 7-8 hours till moisture content

Sources & evidence

ORD record
ord-9f639ba09f4f43f0b359f4a7ae64c9d1
Source dataset
uspto-grants-2012_05
Patent number
US08178674B2

Reaction notes

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