1-Hydroxybenzotriazole → ethyl (3R)-1-(4-((4,4,4-trifluoro-1-(2-methyl-4-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)butyl)amino)benzoyl)piperidine-3-carboxylate

HRID 1520283Notes

Reaction equation

HRID 1520283 reaction equation
[F:1][C:2]([F:33])([F:32])[CH2:3][CH2:4][CH:5]([NH:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=1)[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:20]=[C:19]3[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]3)=[N:13]2)=[CH:8][C:7]=1[CH3:21].[NH:34]1[CH2:39][CH2:38][CH2:37][C@@H:36]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:35]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.O.CN(C=O)C>[F:33][C:2]([F:1])([F:32])[CH2:3][CH2:4][CH:5]([NH:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([N:34]2[CH2:39][CH2:38][CH2:37][C@@H:36]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:35]2)=[O:28])=[CH:25][CH:24]=1)[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:20]=[C:19]3[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]3)=[N:13]2)=[CH:8][C:7]=1[CH3:21]

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1178403544-((4,4,4-trifluoro-1-(2-methyl-4-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)butyl)amino)benzoic acid

Product 1

HCID 131733105ethyl (3R)-1-(4-((4,4,4-trifluoro-1-(2-methyl-4-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)butyl)amino)benzoyl)piperidine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-((4,4,4-trifluoro-1-(2-methyl-4-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)butyl)amino)benzoic acid, ethyl (3R)-piperidine-3-carboxylate (5.24 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.51 g), 1-hydroxybenzotriazole (4.59 g), N,N-diisopropylethylamine (8.90 mL), 4-dimethylaminopyridine (0.208 g) and DMF (42.5 ml) was stirred at room temperature overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (9.61 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-948d17196cfb440a989720eefc7938d0
Source dataset
uspto-grants-2015_07
Patent number
US09073864B2

Reaction notes

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