Diisopropylethylamine → (S)-2-[4-(6,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanol

HRID 131454Notes

Reaction equation

HRID 131454 reaction equation
Cl.[F:2][C:3]1[C:4]([F:19])=[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.C(N(CC)C(C)C)(C)C.[NH:29]1[CH2:34][CH2:33]N[CH2:31][C@@H:30]1[CH2:35][CH2:36][OH:37]>CS(C)=O.C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:33][CH2:34][NH:29][C@@H:30]([CH2:35][CH2:36][OH:37])[CH2:31]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 1519380(S)-2-(Piperazin-2-yl)ethanolHCID 1363885776,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

Product 1

HCID 135401139(S)-2-[4-(6,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanolYield 41.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 22340214Dimethylsulfoxide tolueneSolvent

Conditions

Temperature
120 °C

Procedure

Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.51, 4.99 mmol), N,N-diisopropylethylamine (0.91 mL, 5.24 mmol) and (S)-2-piperazin-2-yl-ethanol (1.3 g, 9.99 mmol) in dimethylsulfoxide/toluene (1:2)(18 ml), stir under nitrogen and heat in an oil bath at 120° C. for 72 hours. Dilute the mixture with water (20 mL) and ethyl acetate (40 mL), separate layers and extract the aqueous with ethyl acetate. Combine all ethyl acetate extracts and wash with water and brine. Dry the organic phase (Na2SO4), filter and concentrate under reduced pressure. Purify by silica gel chromatography (eluent: 0-13% 2N ammonia in methanol/dichloromethane) to give 780 mg of impure product. Purify by silica gel chromatography (eluent: 85% dichloromethane/10% acetonitrile/0%2N ammonia in methanol to 80% dichloromethane/10% acetonitrile/10% 2N ammonia in methanol) to give the title compound (516 mg, 27%): Mass Spectrum (ESMS) 379 (M+1); 377 (M−1).

Workup

  1. customseparate layers
  2. extractionextract the aqueous with ethyl acetate
  3. washwash with water and brine
  4. dry with materialDry the organic phase (Na2SO4)
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify by silica gel chromatography (eluent: 0-13% 2N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-056780a3f2694141babfa2992ca66ad9
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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