Ammonia → HCID 58168987, compound

HRID 38802Notes

Reaction equation

HRID 38802 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]([N:24]4[CH2:29][CH2:28][CH:27]([C:30](O)=[O:31])[CH2:26][CH2:25]4)=[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.F[P-](F)(F)(F)(F)F.[N:40]1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.N>O.C(O)C.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:24]4[CH2:25][CH2:26][CH:27]([C:30]([NH2:40])=[O:31])[CH2:28][CH2:29]4)=[O:23])=[CH:14][N:13]=3)[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2

Participants

8

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58168828HCID 58168828, compound

Product 1

HCID 58168987HCID 58168987, compoundYield 68.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-{[2-(adamantan-1-ylamino)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}piperidine-4-carboxylic acid (100 mg) and N,N-dimethyl formamide (2 mL) were added 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (84 mg) and N,N-diisopropyl ethylamine (77 μL) at room temperature, followed by stirring at the same temperature for 1.5 hours. To the reaction mixture was added 28% aqueous ammonia (2 mL) at room temperature, followed by stirring at the same temperature for 3 hours. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with 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: chloroform-methanol), and the obtained crude product was solidified from a mixed solvent of ethanol and water to obtain 1-{[2-(adamantan-1-ylamino)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}piperidine-4-carboxamide (68 mg) as a white powder.

Workup

  1. stirringby stirring at the same temperature for 3 hours
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent: chloroform-methanol)
  7. customthe obtained crude product

Sources & evidence

ORD record
ord-dc92fbd27efe46a6b027f27b7dd11e50
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

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