1-Azido-2-methoxyethane → 2-Amino-6-(1-(2-methoxyethyl)-1H-1,2,3-triazol-4-yl)benzonitrile

HRID 711906Notes

Reaction equation

HRID 711906 reaction equation
[N:1]([CH2:4][CH2:5][O:6][CH3:7])=[N+:2]=[N-:3].[NH2:8][C:9]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]#[CH:18])[C:10]=1[C:11]#[N:12].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>O.C(O)(C)(C)C.O.[O-]S([O-])(=O)=O.[Cu+2]>[NH2:8][C:9]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:3]=[N:2][N:1]([CH2:4][CH2:5][O:6][CH3:7])[CH:18]=2)[C:10]=1[C:11]#[N:12]

Participants

7

Reactant 3

HCID 128583991-Azido-2-methoxyethaneHCID 23667548Sodium AscorbateHCID 866574822-Amino-6-ethynylbenzonitrile

Product 1

HCID 674000682-Amino-6-(1-(2-methoxyethyl)-1H-1,2,3-triazol-4-yl)benzonitrileYield 88%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

To a solution of 1-bromo-2-methoxyethane (5.00 g, 35.97 mmol) in DMF (25 mL), was added sodium azide (3 equiv.) and the mixture was heated at 50° C. for 48 hours. The reaction mixture was diluted with water (75 mL) and extracted with diethyl ether. The organic extract was dried over MgSO4 and concentrated to furnish 1-azido-2-methoxyethane as a yellow liquid. This azide (200 mg, 1.94 mmol) was added to a solution of 2-Amino-6-ethynylbenzonitrile (250 mg, 1.76 mmol) (Example 267c) in H2O/tert-BuOH=1:2 (15 mL) and the solution was treated consecutively with sodium ascorbate (0.264 mmol) and CuSO4 (0.035 mmol). The reaction mixture was stirred at room temperature for 48 hours, diluted with water and extracted with ethyl acetate. The organic extract was dried over MgSO4 and purified over silica gel (ethyl acetate/hexane 6:4) to furnish the title compound as a white solid in 88% yield. 1H NMR (400 MHz, DMSO-d6) δ 3.26 (s, 3H), 3.78 (t, J=5.2 Hz, 2H), 4.23 (t, J=5.2 Hz, 2H), 6.13 (br s, 2H), 6.80 (dd, J=1.2, 8.4 Hz, 1H), 7.09 (dd, J=1.2, 7.6 Hz, 1H), 7.36 (t, J=8.4 Hz, 1H), 8.52 (s, 1H). MS 244 (MH+).

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. dry with materialwas dried over MgSO4
  4. custompurified over silica gel (ethyl acetate/hexane 6:4)

Sources & evidence

ORD record
ord-34e3396fc08842d487c8c03a6a5fb33e
Source dataset
uspto-grants-2015_11
Patent number
US09181276B2

Reaction notes

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