Triethylamine → HCID 67958770, compound

HRID 72500

Reaction equation

HRID 72500 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([CH:32]=[CH:33][CH:34]=2)[O:17][CH:18]2[CH2:21][N:20]([C:22]3[N:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:23]=3[C:24](O)=[O:25])[CH2:19]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:59][C:60]1([C:63]2[CH:72]=[CH:71][C:66]([C:67]([O:69][CH3:70])=[O:68])=[CH:65][CH:64]=2)[CH2:62][CH2:61]1.C(N(CC)CC)C>CN(C)C=O.O>[Cl:31][C:28]1[CH:27]=[C:23]([C:24](=[O:25])[NH:59][C:60]2([C:63]3[CH:72]=[CH:71][C:66]([C:67]([O:69][CH3:70])=[O:68])=[CH:65][CH:64]=3)[CH2:62][CH2:61]2)[C:22]([N:20]2[CH2:21][CH:18]([O:17][C:16]3[CH:15]=[C:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]4)[CH:34]=[CH:33][CH:32]=3)[CH2:19]2)=[N:30][CH:29]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679581532-(3-(3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid

Product 1

HCID 67958770HCID 67958770, compoundYield 66.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A suspension of 2-(3-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid (D110) (150 mg, 0.306 mmol), 1-Hydroxybenzotriazole hydrate (47 mg, 0.306 mmol) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (88 mg, 0.46 mmol) in dimethylformamide (2 ml) was stirred 40 min at room temperature. A solution of methyl 4-(1-aminocyclopropyl)benzoate (D7) (68.9 mg, 0.306 mmol) and triethylamine (0.042 ml, 0.306 mmol) in dimethylformamide (2 ml) was added and the resulting mixture was stirred 40 min at room temperature. Water (2 ml) was added and the resulting precipitate was collected by filtration and purified by Biotage column (10 g) eluting with a mixture dichloromethane/ethylacetate from 100/0 to 80/20. Collected fractions, after solvent evaporation, afforded tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate (135 mg)

Workup

  1. stirringthe resulting mixture was stirred 40 min at room temperature
  2. filtrationthe resulting precipitate was collected by filtration
  3. custompurified by Biotage column (10 g)
  4. washeluting with a mixture dichloromethane/ethylacetate from 100/0 to 80/20
  5. customCollected fractions, after solvent evaporation

Sources & evidence

ORD record
ord-6fc46c660ee24f5595393423087354ea
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Linked notes

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