HCID 67352602, compound → HCID 59497887, compound

HRID 1676117Notes

Reaction equation

HRID 1676117 reaction equation
C[O:2][C:3](=[O:29])[CH2:4][CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([C:13]2[O:14][C:15]([C:18]3[S:19][C:20]([CH3:27])=[C:21]([CH2:23][CH:24]([CH3:26])[CH3:25])[CH:22]=3)=[N:16][N:17]=2)=[CH:8][C:7]=1[CH3:28]>C(O)=O>[CH2:23]([C:21]1[CH:22]=[C:18]([C:15]2[O:14][C:13]([C:9]3[CH:10]=[C:11]([CH3:12])[C:6]([CH2:5][CH2:4][C:3]([OH:29])=[O:2])=[C:7]([CH3:28])[CH:8]=3)=[N:17][N:16]=2)[S:19][C:20]=1[CH3:27])[CH:24]([CH3:26])[CH3:25]

Participants

3

Reactant 1

HCID 67352602HCID 67352602, compound

Product 1

HCID 59497887HCID 59497887, compound

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

To a solution of 4-(2-tert-butoxycarbonyl-ethyl)-3,5-dimethyl-benzoic acid (763 mg, 3.59 mmol) in DCM (18 mL), DIPEA (542 mg, 4.20 mmol) is added followed by TBTU (1.27 g, 3.95 mmol). The mixture is stirred for 15 min before Intermediate C1 (1.0 g, 3.59 mmol) is added. Stirring is continued at rt for 16 h. The mixture is diluted with diethyl ether, washed with 1 N aq. NaOH solution, then 1 N aq. HCl solution followed by brine, dried over Na2SO4, and filtered. The solvent is evaporated to give 3-{4-[N′-(4-isobutyl-5-methyl-thiophene-2-carbonyl)-hydrazinocarbonyl]-2,6-dimethyl-phenyl}-propionic acid (1.66 g) as a colourless foam; LC-MS: tR=1.09 min, [M+1]=473.48. To a solution of this material in THF (15 mL) Burgess reagent (1.26 g, 5.27 mmol) is added. The mixture is heated to 110° C. for 3 min in a microwave oven. The mixture is cooled to rt, diluted with diethyl ether and washed with 1 N aq. NaOH. The organic extract is dried over Na2SO4, filtered and concentrated to give 3-{4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenyl}-propionic acid methyl ester (1.26 g) as a yellow oil that slowly solidifies; LC-MS: tR=1.24 min, [M+1]=455.21. A suspension of this ester in formic acid (20 mL) is stirred at rt for 3 h. The formic acid is evaporated and the residue is purified by CC on silica gel eluting with DCM containing 5% of methanol to give 3-{4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenyl}-propionic acid as a pale yellow solid; LC-MS: tR=1.07 min, [M+1]=399.16.

Workup

  1. customThe formic acid is evaporated
  2. customthe residue is purified by CC on silica gel eluting with DCM containing 5% of methanol

Sources & evidence

ORD record
ord-782f37c1147d492cb13c0ddcd916e387
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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