Methyl 4-(1-aminocyclopropyl)benzoate hydrochloride → Methyl 4-(1-(5-chloro-2-(3-(3-(trifluoromethyl)phenoxy)azetidin-1-yl)nicotinamido)cyclopropyl)benzoate

HRID 72493Notes

Reaction equation

HRID 72493 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:14][CH:13]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7](O)=[O:8].Cl.[NH2:27][C:28]1([C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=2)[CH2:30][CH2:29]1>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:14][CH:13]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:23])([F:25])[F:24])[CH:17]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7]([NH:27][C:28]1([C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=2)[CH2:30][CH2:29]1)=[O:8]

Participants

3

Reactant 2

HCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679582885-Chloro-2-(3-(3-(trifluoromethyl)phenoxy)azetidin-1-yl)nicotinic acid

Product 1

HCID 67958340Methyl 4-(1-(5-chloro-2-(3-(3-(trifluoromethyl)phenoxy)azetidin-1-yl)nicotinamido)cyclopropyl)benzoateYield 8.7%

Procedure

The title compound (D149) (20 mg) was prepared according to the experimental procedure described in Description 148 starting from 5-chloro-2-(3-(3-(trifluoromethyl)phenoxy)azetidin-1-yl)nicotinic acid (D105) (160 mg, 0.423 mmol) and methyl 4-(1-aminocyclopropyl)benzoate (D7) (115.45 mg, 0.507 mmol). The residue obtained from SPE-Si cartridge purification (38 mg) dissolved in a mixture of chloroform/ethanol/n-hexane (70/15/15) (1 ml) was separated by chiral HPLC [Phenomenex Lux1 column (250×20 mm, 5 μm particle size). Mobile phase: isocratic premixed mixture of (hexane 75%, ethanol 25%) containing 0.1% of diethylamine. Flow rate=10 ml/min. UV detection: 235 nm]. Collected fractions, after solvent evaporation afforded the title compound (D149) (20 mg)

Workup

  1. customThe title compound (D149) (20 mg) was prepared
  2. customThe residue obtained from SPE-
  3. customSi cartridge purification (38 mg)
  4. dissolutiondissolved in a mixture of chloroform/ethanol/n-hexane (70/15/15) (1 ml)
  5. customwas separated by chiral HPLC [Phenomenex Lux1 column (250×20 mm, 5 μm particle size). Mobile phase: isocratic premixed mixture of (hexane 75%, ethanol 25%) containing 0.1% of diethylamine. Flow rate=10 ml/min. UV detection: 235 nm]
  6. customCollected fractions, after solvent evaporation

Sources & evidence

ORD record
ord-44ac184e7d2044e9a14884cac073fc55
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

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