Triethylamine → (4R)-3-Methoxy-N-[(1R,3S)-3-[(3R)-tetrahydrofuran-3-yl]-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]tetrahydro-2H-pyran-4-amine

HRID 1044634Notes

Reaction equation

HRID 1044634 reaction equation
Cl.Cl.[O:3]1[CH2:7][CH2:6][C@H:5]([C@:8]2([C:14]([N:16]3[CH2:21][CH2:20][N:19]([C:22]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=4)[CH2:18][CH2:17]3)=[O:15])[CH2:12][CH2:11][C@@H:10]([NH2:13])[CH2:9]2)[CH2:4]1.[CH3:32][O:33][CH:34]1[C:39](=O)[CH2:38][CH2:37][O:36][CH2:35]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:32][O:33][CH:34]1[C@H:39]([NH:13][C@@H:10]2[CH2:11][CH2:12][C@:8]([C@H:5]3[CH2:6][CH2:7][O:3][CH2:4]3)([C:14]([N:16]3[CH2:17][CH2:18][N:19]([C:22]4[CH:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=4)[CH2:20][CH2:21]3)=[O:15])[CH2:9]2)[CH2:38][CH2:37][O:36][CH2:35]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 68596876(1R,3S)-3-[(3R)-tetrahydrofuran-3-yl]-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride

Product 1

HCID 68932995(4R)-3-Methoxy-N-[(1R,3S)-3-[(3R)-tetrahydrofuran-3-yl]-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]tetrahydro-2H-pyran-4-amineYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R,3S)-3-[(3R)-tetrahydrofuran-3-yl]-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride (73.8 mg, 0.152 mmol), 3-methoxytetrahydro-4H-pyran-4-one (59.4 mg, 0.456 mmol) and triethylamine (0.0848 mL, 0.608 mmol) in dry methylene chloride (4.1 mL) was added sodium triacetoxyborohydride (96.7 mg, 0.456 mmol). After being stirred at room temperature under N2, the reaction was quenched with aqueous NaHCO3 and diluted with CH2C2. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 three times. The organics were combined; dried over MgSO4, filtered, concentrated and purified by silica gel chromatography (Combi-Flash system, 0 to 40% MeOH in EtOAc, gradient, 12 gram column) to provide the desired product (20 mg, 41%). MS calculated for C26H37F3N4O4: (M+H) 527.3; found 527.3.

Workup

  1. customthe reaction was quenched with aqueous NaHCO3
  2. additiondiluted with CH2C2
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 three times
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (Combi-Flash system, 0 to 40% MeOH in EtOAc, gradient, 12 gram column)

Sources & evidence

ORD record
ord-2455b5521a414d54b49de0598101ad7a
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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