Triethylamine → N-[(1R,3S)-3-Isopropyl-3-({4-[5-(trifluoromethyl)pyridin-3-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine

HRID 1044567Notes

Reaction equation

HRID 1044567 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[CH:22]([C@:25]1([C:31]([N:33]2[CH2:38][CH2:37][N:36]([C:39]3[CH:40]=[N:41][CH:42]=C(C(F)(F)F)[CH:44]=3)[CH2:35][CH2:34]2)=[O:32])[CH2:29][CH2:28][C@@H:27]([NH2:30])[CH2:26]1)([CH3:24])[CH3:23].[CH3:49][O:50][CH:51]1[C:56](=O)[CH2:55][CH2:54][O:53][CH2:52]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CCOC(C)=O>[CH:22]([C@:25]1([C:31]([N:33]2[CH2:34][CH2:35][N:36]([C:39]3[CH:40]=[N:41][CH:42]=[C:3]([C:2]([F:7])([F:6])[F:1])[CH:44]=3)[CH2:37][CH2:38]2)=[O:32])[CH2:29][CH2:28][C@@H:27]([NH:30][CH:56]2[CH2:55][CH2:54][O:53][CH2:52][CH:51]2[O:50][CH3:49])[CH2:26]1)([CH3:24])[CH3:23]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 86633369HCID 86633369, compound

Product 1

HCID 57938722N-[(1R,3S)-3-Isopropyl-3-({4-[5-(trifluoromethyl)pyridin-3-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amineYield 82.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1R,3S)-3-isopropyl-3-({4-[5-(trifluoromethyl)pyridin-3-yl]piperazin-1-yl}carbonyl)cyclopentanamine tris(trifluoroacetate) (25 mg, 0.034 mmol), 3-methoxytetrahydro-4H-pyran-4-one (13 mg, 0.10 mmol) and triethylamine (0.024 mL, 0.17 mmol) in methylene chloride (5 mL) was added sodium triacetoxyborohydride (22 mg, 0.10 mmol). The mixture was stirred under N2 at room temperature overnight and diluted with EtOAc. The resulting solution was washed with saturated NaHCO3, dried (MgSO4), and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc to EtOAc/MeOH/Et3N=9:1:0.5) to give 14 mg of desired product as a mixture of two isomers. The two isomers were separated by chiral HPLC to give peak 1 (6.6 mg) and peak 2 (4.7 mg). LCMS calculated for C25H37F3N4O3: (M+1) 499; found 499.2 for both isomers.

Workup

  1. washThe resulting solution was washed with saturated NaHCO3
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography on silica gel (EtOAc to EtOAc/MeOH/Et3N=9:1:0.5)

Sources & evidence

ORD record
ord-fbf8650087bf4b1d84d1ef1cea1c4467
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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