HCID 57722711, compound → {6-Cyano-3-[2,2-difluoro-2-(5-methyl-pyridin-2-yl)-ethylamino]-2-fluoro-phenyl}-acetic acid ethyl ester

HRID 1987050Notes

Reaction equation

HRID 1987050 reaction equation
[F:1][C:2]([F:12])([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][N:6]=1)[CH2:3][NH2:4].[CH2:13]([O:15][C:16](=[O:28])[CH2:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[C:20](F)[C:19]=1[F:27])[CH3:14]>CS(C)=O>[CH2:13]([O:15][C:16](=[O:28])[CH2:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[C:20]([NH:4][CH2:3][C:2]([F:1])([F:12])[C:5]2[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][N:6]=2)[C:19]=1[F:27])[CH3:14]

Participants

4

Reactant 2

HCID 57722711HCID 57722711, compoundHCID 577227152-Pyridineethanamine, beta,beta-difluoro-5-methyl-

Product 1

HCID 57722723{6-Cyano-3-[2,2-difluoro-2-(5-methyl-pyridin-2-yl)-ethylamino]-2-fluoro-phenyl}-acetic acid ethyl esterYield 48.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2,2-Difluoro-2-(5-methyl-pyridin-2-yl)-ethylamine (1.85 g, 10.76 mmol, 2×) and (6-Cyano-2,3-difluoro-phenyl)-acetic acid ethyl ester (1.2 g, 5.33 mmol), prepared as described in Example 2f, was dissolved into DMSO (3 mL) and heated to 90° C. under argon. After 20 h, the reaction was partitioned between EtOAc (50 mL) and H2O (50 mL). The aqueous phase was re-extracted with EtOAc (30 mL) and the combined organic phase dried over Na2SO4 and concentrated to afford a yellow oil. Purification via flash chromatography (20% EtOAc/hexanes) afforded the product as a clear oil (968 mg, 2.57 mmol, 48% yield). 1H NMR (300 Hz, CDCl3) δ 8.49 (s, 1H), 7.59 (m, 2H), 7.30 (m, 1H), 6.79 (t, J=8.2 Hz, 1H), 4.13 (m, 4H), 3.80 (d, J=2.0 Hz, 2H), 2.41 (s, 3H), 1.27 (t, J=6.9 Hz, 3H); LC/MS (m/z) [M+1]+ 378.0 (calculated for C19H19F3N3O2, 378.4).

Workup

  1. customprepared
  2. customthe reaction was partitioned between EtOAc (50 mL) and H2O (50 mL)
  3. extractionThe aqueous phase was re-extracted with EtOAc (30 mL)
  4. dry with materialthe combined organic phase dried over Na2SO4
  5. concentrationconcentrated
  6. customto afford a yellow oil
  7. customPurification via flash chromatography (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2b33b941cbbe44f3ae2d940e73632eb1
Source dataset
uspto-grants-2009_06
Patent number
US07550474B2

Reaction notes

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