1-Bromo-3,6-dioxaheptane → 3-(2-(2-Methoxyethoxy)ethylamino)-5-amino-4-chlorobenzonitrile

HRID 921865Notes

Reaction equation

HRID 921865 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([NH2:11])[C:9]=1[Cl:10])[C:5]#[N:6].Br[CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19]>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([NH:11][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])[C:9]=1[Cl:10])[C:5]#[N:6]

Participants

6

Reactant 2

HCID 1235321-Bromo-3,6-dioxaheptaneHCID 124029953,5-Diamino-4-chlorobenzonitrile

Product 1

HCID 899226323-(2-(2-Methoxyethoxy)ethylamino)-5-amino-4-chlorobenzonitrileYield 28.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3,5-diamino-4-chlorobenzonitrile (220 mg, 1.313 mmol) in DMF (3 mL) was added IIlunig's Base (2.75 mL, 15.75 mmol) followed by 1-bromo-2-(2-methoxyethoxy)ethane (1442 mg, 7.88 mmol). The resulting solution was heated at 100° C. for 16 h. LC-MS indicated ca. 30% conversion. It was diluted with EtOAc and water. After separating the layers, the aqueous layer was further extracted with EtOAc. The combined organic extracts were washed with water, brine, dried over MgSO4, filtered and concentrated. Purification via silica gel chromatography (0-70% EtOAc in Hexanes, 24 g) gave 3-amino-4-chloro-5-((2-(2-methoxyethoxy)ethyl)amino)benzonitrile (100 mg) as an orange oil.

Workup

  1. customAfter separating the layers
  2. extractionthe aqueous layer was further extracted with EtOAc
  3. washThe combined organic extracts were washed with water, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography (0-70% EtOAc in Hexanes, 24 g)

Sources & evidence

ORD record
ord-bdc587d5c255475392306778bfcbba6d
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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