Triethylamine → 7Hydroxy-4-methyl-3-[4-methyl-5-(4-methyl-piperazine-1-carbonyl)-thiazol-2-yl]-chromen-2-one

HRID 579443Notes

Reaction equation

HRID 579443 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH2:8](N(CC)CC)C.[OH:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[C:21]([C:27]3[S:28][C:29]([C:33](O)=[O:34])=[C:30]([CH3:32])[N:31]=3)[C:22](=[O:26])[O:23]2)=[CH:18][CH:17]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C([O-])(O)=O.[Na+]>O.O1CCCC1>[OH:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([CH3:8])=[C:21]([C:27]3[S:28][C:29]([C:33]([N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[O:34])=[C:30]([CH3:32])[N:31]=3)[C:22](=[O:26])[O:23]2)=[CH:18][CH:17]=1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 1363877702-(7-Hydroxy-2-oxo-2H-chromen-3-yl)-4-methyl-thiazole-5-carboxylic acid

Product 1

HCID 1363877737Hydroxy-4-methyl-3-[4-methyl-5-(4-methyl-piperazine-1-carbonyl)-thiazol-2-yl]-chromen-2-oneYield 83.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To dry tetrahydrofuran (12 mL) at 0° C., 1-methylpiperazine (61 μL, 55 mg, 0.55 mmol), triethylamine (210 μL, 152 mg, 1.5 mmol), 2-(7-hydroxy-2-oxo-2H-chromen-3-yl)-4-methyl-thiazole-5-carboxylic acid (156 mg, 0.49 mmol), (3-dimethylamino-propyl)-ethyl-carbodiimid hydrochloride (105 mg, 0.55 mmol) and 1-hydroxybenzotriazole monohydrate (84 mg, 0.55 mmol) were added sequentially, and the mixture was stirred at room temperature for 16 h. After addition of water (30 mL) the pH was adjusted to 8 by addition of a 5% aqueous solution of NaHCO3 and the mixture was extracted with tetrahydrofuran (3×15 mL). After drying (MgSO4) and evaporation, the residue was purified by column chromatography over silica (Kieselgel 60) using chloroform-methanol 9:1 as eluent. The title compound (156 mg, 0.41 mmol, 81%) was obtained as a yellow solid.

Workup

  1. extractionthe mixture was extracted with tetrahydrofuran (3×15 mL)
  2. customAfter drying
  3. custom(MgSO4) and evaporation
  4. customthe residue was purified by column chromatography over silica (Kieselgel 60)

Sources & evidence

ORD record
ord-9fb8210d67924352a8980bdf2c07171b
Source dataset
uspto-grants-2015_05
Patent number
US09040714B2

Reaction notes

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