Methanol → Olanzapine

HRID 425230Notes

Reaction equation

HRID 425230 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.CO.O.[CH3:21][N:22]1[CH2:27][CH2:26]N[CH2:24][CH2:23]1>CS(C)=O>[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[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]3)[C:4]=2[CH:16]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 531671-MethylpiperazineHCID 13552565010H-Thieno[2,3-b][1,5]benzodiazepin-4-amine, 2-methyl-, hydrochloride (1:1)

Product 1

HCID 135398745Olanzapine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
20 °C

Procedure

4-amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine, hydrochloride (50 g) was stirred in a mixture of N-Methylpiperazine (113 g) and Dimethylsulfoxide (300 mL) at 120° C. for 20 h under nitrogen atmosphere. The reaction mass was cooled to 20° C., followed by addition of methanol (500 mL) and the reaction mass was stirred for 30 min. Water (150 mL) was added at 20° C. in 25 min, and the reaction mass was cooled to 5° C. The reaction mass was stirred for 30 min at 0-5° C. The product was filtered and was washed with chilled methanol (50 mL, 5° C.). Dried the product at 50° C. under reduced pressure to give technical 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine or Olanzapine.

Workup

  1. temperaturethe reaction mass was cooled to 5° C
  2. stirringThe reaction mass was stirred for 30 min at 0-5° C
  3. filtrationThe product was filtered
  4. washwas washed with chilled methanol (50 mL, 5° C.)
  5. customDried the product at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-52f8738321334c25b136f78313dd4dc0
Source dataset
uspto-grants-2012_01
Patent number
US08106188B2

Reaction notes

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