1-Hydroxybenzotriazole → N-(2-hydroxy-1-phenylethyl)-4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxamide

HRID 517543Notes

Reaction equation

HRID 517543 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:21](O)=[O:22])[S:5][C:6]=1[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:9]=1.[NH2:24][CH:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:26][OH:27].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O>[OH:27][CH2:26][CH:25]([NH:24][C:21]([C:4]1[S:5][C:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]3)[CH:9]=2)=[C:2]([CH3:1])[N:3]=1)=[O:22])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 924662-Amino-2-phenylethanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867114824-Methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylic acid

Product 1

HCID 86711483N-(2-hydroxy-1-phenylethyl)-4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxamideYield 48.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylic acid (200 mg, 0.6 mmol), 2-amino-2-phenylethanol (99 mg, 0.7 mmol) and TEA (0.3 mL, 1.8 mmol) in DMF (2 mL), EDCI.HCl (175 mg, 0.9 mmol) and HOBT (95 mg, 0.7 mmol) were added. The mixture was stirred at 50° C. overnight, then cooled to RT, diluted with H2O (50 mL) and extracted with DCM/MeOH (10/1, 4×30 mL). The combined organic layers were washed with a saturated aqueous solution of LiCl (3×20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by Combiflash reverse phase chromatography (50%˜60% MeCN/H2O containing 10 mM NH4HCO3) to afford N-(2-hydroxy-1-phenylethyl)-4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxamide as a colorless oil (130 mg, 48%). MS (ES+) C25H30N4O2S requires: 450, found: 451 [M+H]+.

Workup

  1. additionwere added
  2. temperaturecooled to RT
  3. extractionextracted with DCM/MeOH (10/1, 4×30 mL)
  4. washThe combined organic layers were washed with a saturated aqueous solution of LiCl (3×20 mL) and brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product, which
  9. customwas purified by Combiflash reverse phase chromatography (50%˜60% MeCN/H2O containing 10 mM NH4HCO3)

Sources & evidence

ORD record
ord-044858c0874c4bf38b404f776ddc9243
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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