Diisopropylethylamine → 5-(3-Trifluoromethyl-phenyl)-1-isopropyl-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid 4-(N,N,N'-trimethylsulfamimidoyl)-benzylamide

HRID 527365Notes

Reaction equation

HRID 527365 reaction equation
[CH:1]([N:4]1[C:9]([CH3:10])=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:7](=[O:21])[C:6]([C:22](O)=[O:23])=[CH:5]1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:58][CH2:59][C:60]1[CH:65]=[CH:64][C:63]([S:66](=[N:71][CH3:72])([N:68]([CH3:70])[CH3:69])=[O:67])=[CH:62][CH:61]=1>CN(C=O)C.O>[CH3:69][N:68]([CH3:70])[S:66]([C:63]1[CH:64]=[CH:65][C:60]([CH2:59][NH:58][C:22]([C:6]2[C:7](=[O:21])[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:18])([F:20])[F:19])[CH:12]=3)=[C:9]([CH3:10])[N:4]([CH:1]([CH3:2])[CH3:3])[CH:5]=2)=[O:23])=[CH:61][CH:62]=1)(=[N:71][CH3:72])=[O:67]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867115961-Isopropyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acidHCID 899788134-(Aminomethyl)-N,N,N'-trimethylbenzenesulfonimidamide

Product 1

HCID 899786615-(3-Trifluoromethyl-phenyl)-1-isopropyl-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid 4-(N,N,N'-trimethylsulfamimidoyl)-benzylamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1-isopropyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid (preparation 9.2, 186 mg, 0.55 mmol) in DMF (5 mL) is treated with DIPEA (300 μL, 1.72 mmol) and stirred at room temperature for 10 min. HBTU (312 mg, 0.82 mmol) is added, and the mixture is stirred for 20 min. A solution of 4-(aminomethyl)-N,N,N′-trimethylbenzenesulfonimidamide (preparation 60d, 156 mg, 0.69 mmol) in DMF (0.5 mL) is added and the mixture is stirred for 2 h. Water is added and the mixture is extracted with dichloromethane. The organic layer is dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by preparative reversed phase HPLC (Xbridge, gradient of acetonitrile in water, 0.1% TFA). Yield: 41 mg (11% of theory); ESI mass spectrum: [M+H]+=549; r.t. HPLC: 1.17 min (Z001_005).

Workup

  1. stirringthe mixture is stirred for 20 min
  2. stirringthe mixture is stirred for 2 h
  3. extractionthe mixture is extracted with dichloromethane
  4. dry with materialThe organic layer is dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by preparative reversed phase HPLC (Xbridge, gradient of acetonitrile in water, 0.1% TFA)
  7. customr.t
  8. custom1.17 min (Z001_005)

Sources & evidence

ORD record
ord-a4a71a1220a44db8bf4e3e9a58c37b2b
Source dataset
uspto-grants-2016_05
Patent number
US09346794B1

Reaction notes

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