Toluene → HCID 118290407, compound

HRID 628484Notes

Reaction equation

HRID 628484 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[C:25]([N:26]4[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]4)=[CH:24][CH:23]=[CH:22][C:21]=3[CH:33]3[CH2:35][CH2:34]3)=[C:14]([CH3:36])[CH:13]=2)[C:10]=1[CH3:11])=[O:5])[CH3:2].[C:37]1(C)C=CC=CC=1.S(OC)(OC)(=O)=O>O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:37])[N:8]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[C:25]([N:26]4[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]4)=[CH:24][CH:23]=[CH:22][C:21]=3[CH:33]3[CH2:34][CH2:35]3)=[C:14]([CH3:36])[CH:13]=2)[C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6497Dimethyl SulfateHCID 118290393HCID 118290393, compound

Product 1

HCID 118290407HCID 118290407, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

At room temperature, to a mixture of 4-{4-[2-cyclopropyl-6-(4-methyl-5-oxo-4,5-dihydro-tetrazol-1-yl)-benzyloxy]-3-methyl-phenyl}-3-methyl-2,4-dioxo-butyric acid ethyl ester (described in Reference Preparation example 115) 5.5 g, tetrahydrofuran 100 ml was added hydrazine one hydrate 0.56 g and the resulting mixture was stirred for twelve hours. The reaction mixture was concentrated under reduced pressure to give 5-{4-[2-cyclopropyl-6-(4-methyl-5-oxo-4,5-dihydro-tetrazol-1-yl)-benzyloxy]-3-methyl-phenyl}-4-methyl-2H-pyrazole-3-carboxylic acid ethyl ester crude product 5 g. Next, the mixture of the above-mentioned 5-{4-[2-cyclopropyl-6-(4-methyl-5-oxo-4,5-dihydro-tetrazol-1-yl)-benzyloxy]-3-methyl-phenyl}-4-methyl-2H-pyrazole-3-carboxylic acid ethyl ester crude product 5 g, toluene 70 ml and dimethyl sulfate 3.8 g was stirred at 100° C. for three hours. To the reaction mixture was added water and was extracted with ethyl acetate. The organic layer was washed with water and was dried over anhydrous magnesium sulfate, and was then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 5-{4-[2-cyclopropyl-6-(4-methyl-5-oxo-4,5-dihydro-tetrazol-1-yl)-benzyloxy]-3-methyl-phenyl}-2,4-dimethyl-2H-pyrazole-3-carboxylic acid ethyl ester 1.4 g (hereinafter, referred to as “Present compound 48”).

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materialwas dried over anhydrous magnesium sulfate
  4. concentrationwas then concentrated under reduced pressure

Sources & evidence

ORD record
ord-4d334b7a197f4ba8b5713ce58c1faeda
Source dataset
uspto-grants-2016_04
Patent number
US09314023B2

Reaction notes

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