Triethylamine → (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid dimethylamide

HRID 409440Notes

Reaction equation

HRID 409440 reaction equation
[N+](C1C=CC([O:10][C:11]([N:13]2[CH2:17][C@@H:16]([N:18]([CH2:31][C:32]3[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=3)[C:19]3[N:24]=[CH:23][C:22]([C:25]4[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=4)=[CH:21][N:20]=3)[CH2:15][C@H:14]2[CH2:46][CH3:47])=O)=CC=1)([O-])=O.Cl.COC([C@H]1CC[C@H](CN)CC1)=O.[CH2:61]([N:63](CC)[CH2:64]C)C.[Cl-].[NH4+]>CN(C=O)C>[CH3:61][N:63]([CH3:64])[C:11]([N:13]1[CH2:17][C@@H:16]([N:18]([CH2:31][C:32]2[CH:33]=[C:34]([C:42]([F:43])([F:45])[F:44])[CH:35]=[C:36]([C:38]([F:41])([F:39])[F:40])[CH:37]=2)[C:19]2[N:24]=[CH:23][C:22]([C:25]3[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=3)=[CH:21][N:20]=2)[CH2:15][C@H:14]1[CH2:46][CH3:47])=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 59614333(2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 4-nitro-phenyl esterHCID 178501119HCID 178501119, compound

Product 1

HCID 42632980(2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid dimethylamideYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 4-nitro-phenyl ester (0.03 mmol, 20 mg) in 1 mL of DMF are added trans-4-(aminomethyl)cyclohexanecarboxylic acid methyl ester hydrochloride (0.04 mmol, 8 mg) and triethylamine (0.07 mmol, 0.01 mL). The mixture is stirred under microwave irradiation (150° C., 5 bar), then cooled to room temperature. The mixture is poured into a saturated aqueous ammonium chloride and extracted with dichloromethane. The combined organic phases is washed by water and brine, dried over anhydrous Na2SO4 and evaporated. The obtained residue is purified by column chromatography on silica gel (eluent: n-hexane-ethyl acetate) to obtain 12.3 mg (59%) of (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid dimethylamide as colorless oil. ESI-MS m/z: 570 [M+1]+, Retention time 4.05 min (condition B).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with dichloromethane
  3. washThe combined organic phases is washed by water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated
  6. customThe obtained residue is purified by column chromatography on silica gel (eluent: n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a38f485ccd2d4da4a121380140942a2a
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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