Cesium carbonate → HCID 57800471, compound

HRID 1188582Notes

Reaction equation

HRID 1188582 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:26][C:27]1[N:28]=[CH:29][S:30][CH:31]=1>C(#N)C>[CH2:1]([C:4]1[N:5]([CH2:26][C:27]2[N:28]=[CH:29][S:30][CH:31]=2)[C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:15])([F:16])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 98989844-(Bromomethyl)thiazoleHCID 674051552-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 57800471HCID 57800471, compoundYield 82.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 153A) (0.150 g, 0.595 mmol) in anhydrous acetonitrile (25 mL) was added Cs2CO3 (1.90 g, 0.0595 mmol) and 4-(bromomethyl)-1,3-thiazole (0.159 g, 0.893 mmol). The mixture was heated under N2, for 2 h. Upon cooling, the mixture was partitioned between EtOAc and water. The organic phase was separated, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient) to afford a pure product (0.171 g, 82% yield): 1H NMR (400 MHz, CDCl3) δ 8.81-8.80 (d, J=4.0 Hz, 1H), 7.78 (m, 2H), 6.68 (d, J=4.0 Hz, 1H), 6.63 (s, 1H), 5.51 (s, 2H), 2.80-2.76 (t, J=8.0 Hz, 2H), 1.82-1.76 (q, J=8.0 Hz, 2H), 1.06-1.02 (t, J=8.0 Hz, 3H).

Workup

  1. temperatureThe mixture was heated under N2, for 2 h
  2. temperatureUpon cooling
  3. customthe mixture was partitioned between EtOAc and water
  4. customThe organic phase was separated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-9826fbb022a84a839daee50ea81847af
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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