Triethylamine → HCID 57938715, compound

HRID 1044600Notes

Reaction equation

HRID 1044600 reaction equation
Cl.Cl.[CH:3]([C@:6]1([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][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[N:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:23]=[CH:22][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 68595767HCID 68595767, compound

Product 1

HCID 57938715HCID 57938715, compoundYield 83.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride (135.0 mg, 0.2945 mmol), 3-methoxytetrahydro-4H-pyran-4-one (110 mg, 0.88 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), 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 (65 mg after converting to TFA salt) and isomer 2 (45 mg after converting to TFA salt). LCMS calculated for C24H36F3N5O3: (M+1) 500; found 500.1 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-242f08c42b1d4a81bb761d17cfc6ba33
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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