Diisopropylethylamine → 6-Methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

HRID 512491Notes

Reaction equation

HRID 512491 reaction equation
[CH3:1][C:2]1[NH:7][CH:6]=[C:5]([C:8]([OH:10])=O)[C:4](=[O:11])[C:3]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[CH3:56][S:57]([C:60]1[CH:67]=[CH:66][C:63]([CH2:64][NH2:65])=[CH:62][CH:61]=1)(=[O:59])=[O:58]>CN1C(=O)CCC1.CO.O>[CH3:56][S:57]([C:60]1[CH:67]=[CH:66][C:63]([CH2:64][NH:65][C:8]([C:5]2[C:4](=[O:11])[C:3]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:19])[F:21])[CH:13]=3)=[C:2]([CH3:1])[NH:7][CH:6]=2)=[O:10])=[CH:62][CH:61]=1)(=[O:58])=[O:59]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27292694-Methylsulfonylbenzylamine hydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867115326-Methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid

Product 1

HCID 867115336-Methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid (preparation 5b, 3.00 g, 10.1 mmol), HBTU (4.00 g, 10.5 mmol), DIPEA (5.00 mL, 29.4 mmol) in NMP (15 mL) is stirred for 30 min. Then, 4-methylsulfonylbenzylamine hydrochloride (2.46 g, 11.1 mmol) is added and the reaction mixture is stirred for 72 h at room temperature. Water is added to the reaction mixture. The formed gummy precipitate is dissolved in MeOH and purified by preparative reversed-phase HPLC (Gilson, XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.). Yield: 1.50 g (32% of theory); ESI mass spectrum: [M+H]+=465; Retention time HPLC: 0.89 min (Z003—001).

Workup

  1. custompurified by preparative reversed-phase HPLC (Gilson, XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.)
  2. custom0.89 min (Z003—001)

Sources & evidence

ORD record
ord-4f7489c0da5f4e42bb343e578e7fbfef
Source dataset
uspto-grants-2015_08
Patent number
US09102624B2

Reaction notes

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