1-Hydroxybenzotriazole → HCID 58168904, compound

HRID 38778Notes

Reaction equation

HRID 38778 reaction equation
[C:1]12([NH:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[C:15]([C:22](O)=[O:23])=[CH:14][N:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.Cl.[F:26][C:27]([F:35])([F:34])[CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>O.CN(C)C=O>[C:1]12([NH:11][C:12]3[N:17]=[C:16]([C:18]([F:19])([F:21])[F:20])[C:15]([C:22]([N:31]4[CH2:32][CH2:33][CH:28]([C:27]([F:35])([F:34])[F:26])[CH2:29][CH2:30]4)=[O:23])=[CH:14][N:13]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 58168721HCID 58168721, compound

Product 1

HCID 58168904HCID 58168904, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2-(adamantan-1-ylamino)-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (120 mg) and N,N-dimethyl formamide (2.4 mL) were added 4-(trifluoromethyl)piperidine hydrochloride (87 mg), 1-hydroxybenzotriazole (62 mg), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (88 mg), and N,N-diisopropyl ethylamine (0.12 mL) in this order at room temperature, and then the mixture was stirred at room temperature for 16 hours. To the reaction mixture were added a saturated aqueous sodium hydrogen carbonate solution and water, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate), and the obtained white solid was first dissolved in a mixed solvent of hexane and ethyl acetate, and then solidified again to obtain N-adamantan-1-yl-4-(trifluoromethyl)-5-{[4-(trifluoromethyl)piperidin-1-yl]carbonyl}pyrimidin-2-amine (81 mg) as a white powder.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. washThe organic layer 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 obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)
  6. dissolutionthe obtained white solid was first dissolved in a mixed solvent of hexane and ethyl acetate

Sources & evidence

ORD record
ord-37f037b622fc4a1e9411cf402c39489c
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

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