Triethylamine → N-[(1R,3S)-3-Isopropyl-3-({4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine

HRID 1436797Notes

Reaction equation

HRID 1436797 reaction equation
Cl.Cl.[CH:3]([C@:6]1([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[N:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH2:10][CH2:9][C@@H:8]([NH2:11])[CH2:7]1)([CH3:5])[CH3:4].[CH3:30][O:31][CH:32]1[C:37](=O)[CH2:36][CH2:35][O:34][CH2:33]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:3]([C@:6]1([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:27])[F:28])[N:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH2:10][CH2:9][C@@H:8]([NH:11][CH:37]2[CH2:36][CH2:35][O:34][CH2:33][CH:32]2[O:31][CH3:30])[CH2:7]1)([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 68597226(1R,3S)-3-isopropyl-3-(4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride

Product 1

HCID 57938704N-[(1R,3S)-3-Isopropyl-3-({4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amineYield 102.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R,3S)-3-isopropyl-3-(4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride (110 mg, 0.24 mmol), 3-methoxytetrahydro-4H-pyran-4-one (80 mg, 0.61 mmol), and triethylamine (0.16 mL, 1.2 mmol) in methylene chloride (8 mL) was added sodium triacetoxyborohydride (190 mg, 0.88 mmol). After being stirred at room temperature overnight, the reaction was quenched with saturated NaHCO3. The resulting solution was extracted with EtOAc three times. The combined organic layers were dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc to EtOAc/Et3N=10:0.1) to give 123 mg of desired product as a mixture of two isomers. The two isomers were separated by chiral HPLC to give isomer 1 (45 mg after converting to TFA salt) and isomer 2 (35 mg after converting to TFA salt). LCMS calculated for C25H37F3N4O3: (M+H) 498.2; found 498.2 for both isomers.

Workup

  1. customthe reaction was quenched with saturated NaHCO3
  2. extractionThe resulting solution was extracted with EtOAc three times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on silica gel (EtOAc to EtOAc/Et3N=10:0.1)

Sources & evidence

ORD record
ord-c3177fe9b40241e3bcf8d9ebdc45ef43
Source dataset
uspto-grants-2009_11
Patent number
US07618970B2

Reaction notes

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