Dimethyl Sulfoxide → (S)-6-Fluoro-10-[3-(2-hydroxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131449Notes

Reaction equation

HRID 131449 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]2[N:15]=[C:14]([NH2:16])[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1.[NH:19]1[CH2:24][CH2:23]N[CH2:21][C@@H:20]1[CH2:25][CH2:26][OH:27].C(N(C(C)C)CC)(C)C.CS(C)=O>C(OCC)(=O)C.C1(C)C=CC=CC=1>[NH3:8].[CH3:26][OH:27].[F:2][C:3]1[CH:4]=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:23][CH2:24][NH:19][C@@H:20]([CH2:25][CH2:26][OH:27])[CH2:21]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 1519380(S)-2-(Piperazin-2-yl)ethanolHCID 692119036-Fluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

Product 2

HCID 10044077(S)-6-Fluoro-10-[3-(2-hydroxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azuleneYield 28%HCID 21705897Ammonia methanol

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 6-fluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (2.94 g, 10.35 mmol), (S)-2-piperazin-2-yl-ethanol (2.7 g, 20.7 mmol), diisopropylethylamine (3.6 mL, 20.7 mmol), dimethyl sulfoxide (4.25 mL) and toluene (17 mL) and heat to 110° C. for 42 hours. Cool to ambient temperature and dilute with ethyl acetate (200 mL). Wash with saturated sodium bicarbonate solution, brine and evaporate to give 2.64 g of the crude product. Silica gel chromatography, eluting with methylene chloride: acetonitrile: 7N NH3/methanol (85:10:7), gives 0.523 g of the title compound as a brown solid foam: mass spectrum (ion spray): m/z=361 (M+1).

Workup

  1. washWash with saturated sodium bicarbonate solution, brine
  2. customevaporate
  3. customto give 2.64 g of the crude product
  4. washSilica gel chromatography, eluting with methylene chloride

Sources & evidence

ORD record
ord-376ab5033b284ce7ac771b924aca48d6
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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