Potassium tert-butoxide → 4-(4-Cyano-2-methoxyphenyl)-6-ethyl-5-(4-methyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)-1,4-dihydro-pyridine-3-carbonitrile

HRID 1951553Notes

Reaction equation

HRID 1951553 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[CH:11]=[C:12]([C:17]1[S:18][CH:19]=[C:20]([CH3:22])[N:21]=1)[C:13](=O)[CH2:14][CH3:15])[C:6]#[N:7].[NH2:23][C:24]([C:28]([F:31])([F:30])[F:29])=[CH:25][C:26]#[N:27].CC(C)([O-])C.[K+]>C(O)(C)C>[C:6]([C:5]1[CH:8]=[CH:9][C:10]([CH:11]2[C:12]([C:17]3[S:18][CH:19]=[C:20]([CH3:22])[N:21]=3)=[C:13]([CH2:14][CH3:15])[NH:23][C:24]([C:28]([F:31])([F:30])[F:29])=[C:25]2[C:26]#[N:27])=[C:3]([O:2][CH3:1])[CH:4]=1)#[N:7]

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 534010963-Amino-4,4,4-trifluorobut-2-enenitrileHCID 670179833-Methoxy-4-[2-(4-methyl-1,3-thiazol-2-yl)-3-oxopent-1-en-1-yl]benzonitrile

Product 1

HCID 1358449704-(4-Cyano-2-methoxyphenyl)-6-ethyl-5-(4-methyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)-1,4-dihydro-pyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

150 mg (0.480 mmol) of the compound from example 20A, 65 mg (0.480 mmol) of 3-amino-4,4,4-trifluorobut-2-enenitrile [preparation in analogy to U.S. Pat. No. 3,635,977 and K. Krespan, J. Org. Chem. 34, 42-45 (1969)] and 8.1 mg (0.072 mmol) of potassium tert-butoxide are dissolved in 4 ml of isopropanol and stirred at the reflux temperature overnight. After cooling to room temperature, the volatile components are removed in a rotary evaporator, and the crude material is purified initially by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5) and then by MPLC (Biotage 12M cartridge, eluent: isohexane/ethyl acetate 80:20). 25 mg (12% of theory) of the title compound are obtained.

Workup

  1. customthe volatile components are removed in a rotary evaporator
  2. customthe crude material is purified initially by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)

Sources & evidence

ORD record
ord-a74e8910efe64945b44ee158372592e3
Source dataset
uspto-grants-2013_03
Patent number
US08404723B2

Reaction notes

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