Sodium hydride → 1-((3-amino-2-cyanophenoxy)methyl)-N-propylcyclopropanecarboxamide

HRID 711799Notes

Reaction equation

HRID 711799 reaction equation
[OH:1][CH2:2][C:3]1([C:6]([NH:8][CH2:9][CH2:10][CH3:11])=[O:7])[CH2:5][CH2:4]1.[H-].[Na+].[NH2:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19](F)[C:16]=1[C:17]#[N:18]>C1COCC1>[NH2:14][C:15]1[C:16]([C:17]#[N:18])=[C:19]([CH:20]=[CH:21][CH:22]=1)[O:1][CH2:2][C:3]1([C:6]([NH:8][CH2:9][CH2:10][CH3:11])=[O:7])[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5226592-Amino-6-fluorobenzonitrileHCID 667460451-(hydroxymethyl)-N-propylcyclopropanecarboxamide

Product 1

HCID 667463181-((3-amino-2-cyanophenoxy)methyl)-N-propylcyclopropanecarboxamideYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 1-(hydroxymethyl)-N-propylcyclopropanecarboxamide (Example 198c) (0.67 g, 4.25 mmol) in anhydrous THF (10 mL) was treated with NaH (0.17 g, 4.25 mmol, 60% suspension in mineral oil) at 0° C., under a nitrogen atmosphere. The obtained mixture was stirred at 0° C. for 10 min and at rt over 30 min. Then, a solution of 2-amino-6-fluorobenzonitrile (0.53 g, 3.86 mmol) in THF (5.0 mL) was added and the obtained mixture was heated at reflux overnight. The cold mixture was quenched with saturated aqueous solution of NH4Cl (20 mL) and extracted with EtOAc (3×50 mL). The combined extract was washed with brine, dried over anhydrous MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel using gradient hexanes→hexanes/EtOAc (4:6), to give 0.75 g (71%) of the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 7.51 (t, J=6.0 Hz, 1H), 7.17 (t, J=8.0 Hz, 1H), 6.34 (d, J=8.4 Hz, 1H), 6.19 (d, J=8.4 Hz, 1H), 5.97 (broad s, 2H), 4.13 (s, 2H), 3.04 (q, J=6.4 Hz, 2H), 1.43 (hex, J=6.8 Hz, 2H), 1.05-1.11 (m, 2H), 0.78-0.86 (m, 5H).

Workup

  1. temperaturethe obtained mixture was heated
  2. temperatureat reflux overnight
  3. customThe cold mixture was quenched with saturated aqueous solution of NH4Cl (20 mL)
  4. extractionextracted with EtOAc (3×50 mL)
  5. extractionThe combined extract
  6. washwas washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by chromatography on silica gel using gradient hexanes→hexanes/EtOAc (4:6)

Sources & evidence

ORD record
ord-ceac2f090d7842a2a32512e676b4ebc4
Source dataset
uspto-grants-2015_11
Patent number
US09181276B2

Reaction notes

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