Dimethyl Sulfoxide → Olanzapine

HRID 425229Notes

Reaction equation

HRID 425229 reaction equation
Cl.[NH2:2][C:3]1[C:4]2[CH:16]=[C:15]([CH3:17])[S:14][C:5]=2[NH:6][C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=1.CS(C)=O.[C:22]1([CH3:28])C=CC=CC=1.O>CN1CCNCC1>[CH3:17][C:15]1[S:14][C:5]2[NH:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[N:9]=[C:3]([N:2]3[CH2:28][CH2:22][N:6]([CH3:7])[CH2:5][CH2:4]3)[C:4]=2[CH:16]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 1140TolueneHCID 13552565010H-Thieno[2,3-b][1,5]benzodiazepin-4-amine, 2-methyl-, hydrochloride (1:1)

Product 1

HCID 135398745Olanzapine

Reagents, catalysts & solvents 1

HCID 531671-MethylpiperazineSolvent

Conditions

Temperature
50 °C

Procedure

4-Amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine, hydrochloride (100 g) was refluxed in a mixture of N-methylpiperazine (349 mL), dimethylsulphoxide (465 mL) and toluene (465 mL) under a nitrogen atmosphere for 20 hours. The mixture was cooled to 50° C., and water (465 mL) was added at 50-55° C. in 20 min. Then the reaction mass was cooled to 5° C. and stirred for 2 h. The product was filtered and washed with water (100 mL, 20° C.). Dried the product at 60-70° C. under reduced pressure to give crude 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine or Olanzapine.

Workup

  1. temperatureThen the reaction mass was cooled to 5° C.
  2. filtrationThe product was filtered
  3. washwashed with water (100 mL, 20° C.)
  4. customDried the product at 60-70° C. under reduced pressure

Sources & evidence

ORD record
ord-9a22724eeaae4377a527b7de9cebd067
Source dataset
uspto-grants-2012_01
Patent number
US08106188B2

Reaction notes

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