1-Hydroxybenzotriazole → Methyl 2-{[(4-{2-[(2,4-difluorobenzyl)(heptyl)amino]-2-oxoethyl}phenyl)thio]methyl}benzoate

HRID 899869Notes

Reaction equation

HRID 899869 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:22]=[CH:21][CH:20]=[CH:19][C:6]=1[CH2:7][S:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=O)=[CH:11][CH:10]=1)=[O:4].[F:23][C:24]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:25]=1[CH2:26][NH:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:23][C:24]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:25]=1[CH2:26][N:27]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[C:16](=[O:18])[CH2:15][C:12]1[CH:11]=[CH:10][C:9]([S:8][CH2:7][C:6]2[CH:19]=[CH:20][CH:21]=[CH:22][C:5]=2[C:3]([O:2][CH3:1])=[O:4])=[CH:14][CH:13]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 60663854N-(2,4-difluorobenzyl)-N-heptylamineHCID 69120445(4-{[2-(Methoxycarbonyl)benzyl]thio}phenyl)acetic acid

Product 1

HCID 69120607Methyl 2-{[(4-{2-[(2,4-difluorobenzyl)(heptyl)amino]-2-oxoethyl}phenyl)thio]methyl}benzoateYield 77.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(4-{[2-(Methoxycarbonyl)benzyl]thio}phenyl)acetic acid (581 mg, 1.836 mmol) and N-(2,4-difluorobenzyl)-N-heptylamine (465.3 mg, 1.968 mmol) were combined in DMF and the mixture was cooled in an ice-bath. HOBT (260.6 mg, 1.928 mmol) and TBTU (619 mg, 1.928 mmol) were added, followed by DIPEA (747.7 mg 5.785 mmol). The mixture was stirred at room temperature overnight and then evaporated. The resulting mixture was partitioned between ethyl acetate and sodium hydrogencarbonate aqueous solution (sat.). The aqueous portion was extracted with ethyl acetate and the combined organic extracts was dried with magnesium sulphate and then evaporated. Chromatography of the residue on a column (ISOLUTE® SI, 20 g/70 ml) using ethyl acetate/heptane (5:95, then 10:90) as eluant gave 767 mg the desired product, yield 77%.

Workup

  1. temperaturethe mixture was cooled in an ice-bath
  2. customevaporated
  3. customThe resulting mixture was partitioned between ethyl acetate and sodium hydrogencarbonate aqueous solution (sat.)
  4. extractionThe aqueous portion was extracted with ethyl acetate
  5. dry with materialthe combined organic extracts was dried with magnesium sulphate
  6. customevaporated

Sources & evidence

ORD record
ord-86778b2ba32f4adf8e46b31abd75301b
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

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