1-Hydroxybenzotriazole → 5-{1-[4-(3-Chlorophenyl)-3-oxo-piperazin-1-yl]methanoyl}-3-(4-cyanophenyl)-2,3-dihydro-imidazo[2,1-b]thiazole hydrochloride

HRID 844274Notes

Reaction equation

HRID 844274 reaction equation
Cl.[C:2]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:14][S:13][C:12]3=[N:15][CH:16]=[C:17]([C:18]([OH:20])=O)[N:11]23)=[CH:6][CH:5]=1)#[N:3].Cl.[Cl:22][C:23]1[CH:24]=[C:25]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][C:30]2=[O:35])[CH:26]=[CH:27][CH:28]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>>[ClH:22].[Cl:22][C:23]1[CH:24]=[C:25]([N:29]2[CH2:34][CH2:33][N:32]([C:18]([C:17]3[N:11]4[C:12]([S:13][CH2:14][CH:10]4[C:7]4[CH:6]=[CH:5][C:4]([C:2]#[N:3])=[CH:9][CH:8]=4)=[N:15][CH:16]=3)=[O:20])[CH2:31][C:30]2=[O:35])[CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 101311131-(3-chlorophenyl)piperazin-2-one HydrochlorideHCID 699341033-(4-Cyanophenyl)-2,3-dihydro-imidazo[2,1-b]thiazole-5-carboxylic acid hydrochloride

Product 1

HCID 226125285-{1-[4-(3-Chlorophenyl)-3-oxo-piperazin-1-yl]methanoyl}-3-(4-cyanophenyl)-2,3-dihydro-imidazo[2,1-b]thiazole hydrochloride

Procedure

The carboxylic acid from Step D (5.14 g, 16.1 mmol), 1-(3-chlorophenyl)piperazin-2-one hydrochloride (3.97 g, 16.1 mmol) (prepared as described in U.S. Pat. No. 5,856,326), EDC hydrochloride (3.70 g, 19.3 mmol), HOBT (2.61 g, 19.3 mmol), and N,N-diisopropylethylamine (14.0 mL, 80.4 mmol) were stirred in dry, degassed DMF (50 mL) at 25° C. for 16 hours. The reaction was poured onto saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide a yellow oil. The crude product was purified by column chromatography (3→5% methanol/methylene chloride) and converted to the HCl salt to provide the title compound as a yellow solid.

Workup

  1. customin dry
  2. customdegassed DMF (50 mL) at 25° C. for 16 hours
  3. additionThe reaction was poured onto saturated aqueous sodium bicarbonate solution
  4. extractionextracted with methylene chloride (3×100 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a yellow oil
  10. customThe crude product was purified by column chromatography (3→5% methanol/methylene chloride)

Sources & evidence

ORD record
ord-467b5b7b97fc47bd94ad485fbba34073
Source dataset
uspto-grants-2002_04
Patent number
US06380228B1

Reaction notes

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