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 1436767Notes

Reaction equation

HRID 1436767 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.FC(F)(F)[C:10](O)=[O:11].F[C:16](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:43]([C:45]([F:48])([F:47])[F:46])[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].C(N([CH2:54][CH3:55])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[CH2:38][CH2:37][N:36]([C:39]3[CH:40]=[N:41][CH:42]=[C:43]([C:45]([F:48])([F:46])[F:47])[CH:44]=3)[CH2:35][CH2:34]2)=[O:32])[CH2:29][CH2:28][C@@H:27]([NH:30][CH:16]2[CH2:2][CH2:3][O:5][CH2:55][CH:54]2[O:11][CH3:10])[CH2:26]1)([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 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-1yl}carbonyl)cyclopentanamine tris(trifluoroacetate) (25 mg, 0.034 mmol) , 3-methoxytetradyro4H-pyran-4one (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-21a49d6afc8248eba5ab24b67200a0e9
Source dataset
uspto-grants-2009_11
Patent number
US07618970B2

Reaction notes

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