Dimethylformamide → HCID 68554418, compound

HRID 2382131Notes

Reaction equation

HRID 2382131 reaction equation
[H-].[Na+].[CH:3]1([C:6]2[NH:7][C:8]3[C:13]([CH:14]=2)=[CH:12][C:11]([F:15])=[CH:10][CH:9]=3)[CH2:5][CH2:4]1.C[N:17](C=O)C>>[CH:3]1([C:6]2[N:7]([NH2:17])[C:8]3[C:13]([CH:14]=2)=[CH:12][C:11]([F:15])=[CH:10][CH:9]=3)[CH2:5][CH2:4]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 685530852-cyclopropyl-5-fluoro-1H-indole

Product 1

HCID 68554418HCID 68554418, compoundYield 70%

Conditions

Temperature
0 °C

Procedure

A suspension of NaH (1.9 g, 47 mmol, 60% in mineral oil) in DMF (20 mL) at 0° C. is treated with 2-cyclopropyl-5-fluoro-1H-indole (550 mg, 3.14 mmol) and stirred at 0° C. for 1 h. The mixture is treated with HOSA (1.8 g, 15.7 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice, filtered through a pad of Celite, and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 5%-35% EtOAc in heptane to afford 2-cyclopropyl-5-fluoro-indol-1-ylamine (420 mg, 70%). MS: 191 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.30 (m, 1H), 7.11 (m, 1H), 6.92 (m, 1H), 5.90 (s, 1H), 4.57 (s, NH2, 2H), 2.07 (m, 1H), 1.02 (m, 2H), 0.75 (m, 2H).

Workup

  1. additionThe mixture is treated with HOSA (1.8 g, 15.7 mmol) portion wise
  2. temperaturewarmed to rt over 2 h
  3. additionThe mixture is then poured over ice
  4. filtrationfiltered through a pad of Celite
  5. extractionextracted with EtOAc (3×50 mL)
  6. dry with materialThe combined organic layer is dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with 5%-35% EtOAc in heptane

Sources & evidence

ORD record
ord-826dc192de9f4937bfc54fdda70a56f3
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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