Triethylamine → HCID 67958748, compound

HRID 72512Notes

Reaction equation

HRID 72512 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:14][CH:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[F:23])[CH2:12]2)=[C:6]([CH:10]=1)[C:7](O)=[O:8].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:48][C:49]1([C:52]2[CH:61]=[CH:60][C:55]([C:56]([O:58][CH3:59])=[O:57])=[CH:54][CH:53]=2)[CH2:51][CH2:50]1.C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:12][CH:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[F:23])[CH2:14]2)=[C:6]([CH:10]=1)[C:7]([NH:48][C:49]1([C:52]2[CH:61]=[CH:60][C:55]([C:56]([O:58][CH3:59])=[O:57])=[CH:54][CH:53]=2)[CH2:51][CH2:50]1)=[O:8]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679580805-Chloro-2-(3-((2,4-difluorophenyl)amino)azetidin-1-yl)nicotinic acid

Product 1

HCID 67958748HCID 67958748, compoundYield 173.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 5-chloro-2-(3-((2,4-difluorophenyl)amino)azetidin-1-yl)nicotinic acid (D118) (40 mg, 0.118 mmol), 1-Hydroxybenzotriazole hydrate (18 mg, 0.118 mmol) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (34 mg, 0.177 mmol) in dimethylformamide (5 ml) was stirred 10 min at room temperature. A solution of methyl 4-(1-aminocyclopropyl)benzoate hydrochloride (D7) (32.2 mg, 0.141 mmol) and triethylamine (0.02 ml, 0.141 mmol) in dry dimethylformamide (2 ml) was added and the mixture was stirred 24 h at room temperature. After solvent evaporation, water (10 ml) was added and the formed precipitate was filtered off and purified by Biotage SNAP-Si (10 g) cartridge eluting with a mixture dichloromethane/methanol from 100/0 to 80/20. Collected fractions, after solvent evaporation afforded the title compound (D169) (105 mg).

Workup

  1. stirringthe mixture was stirred 24 h at room temperature
  2. customAfter solvent evaporation, water (10 ml)
  3. additionwas added
  4. filtrationthe formed precipitate was filtered off
  5. custompurified by Biotage SNAP-Si (10 g) cartridge
  6. washeluting with a mixture dichloromethane/methanol from 100/0 to 80/20
  7. customCollected fractions, after solvent evaporation

Sources & evidence

ORD record
ord-f9fd8496b8c24567963244c5777053ad
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

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