Ammonia methanol → Olanzamine

HRID 1350359Notes

Reaction equation

HRID 1350359 reaction equation
Cl.[CH3:2][C:3]1[S:12][C:11]2[NH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[N:7]=[C:6]([NH2:17])[C:5]=2[CH:4]=1.N.CO>ClCCl>[CH3:2][C:3]1[S:12][C:11]2[NH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[N:7]=[C:6]([NH2:17])[C:5]=2[CH:4]=1

Participants

4

Reactant 2

HCID 21705897Ammonia methanolHCID 13552565010H-Thieno[2,3-b][1,5]benzodiazepin-4-amine, 2-methyl-, hydrochloride (1:1)

Product 1

HCID 135446208Olanzamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 2-methyl-4H-3-thia-4,9-diazabenzo[f]azulen-10-ylamine hydrochloride (6 g, 22.6 mmoles) in a 5:1 mixture of dichloromethane and commercial 7N ammonia-methanol, wash with half a volume of 5N aqueous sodium hydroxide. Separate the organic layer and extract the aqueous layer twice with dichloromethane. Combine all organic extracts, dry over magnesium sulfate, filter and concentrate in vacuo to yield the title free base as an orange solid: 1H NMR (DMSO-d6): δ8.10–7.80 (br, 1H), 7.30–6.90 (br, 2H), 6.80–6.65 (m, 3H), 6.59 (br dd, 1H, J=7.6, 1.6 Hz), 6.52 (br s, 1H), 2.22 (br s, 3H).

Workup

  1. washwash with half a volume of 5N aqueous sodium hydroxide
  2. customSeparate the organic layer
  3. extractionextract the aqueous layer twice with dichloromethane
  4. dry with materialCombine all organic extracts, dry over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-da6a9e3f51034cf0b3b9c2c1df80dd38
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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