Dimethylformamide → HCID 68555496, compound

HRID 2382113Notes

Reaction equation

HRID 2382113 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[NH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C[N:27](C=O)C>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]=[C:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[N:16]([NH2:27])[CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 59650949HCID 59650949, compound

Product 1

HCID 68555496HCID 68555496, compoundYield 94%

Procedure

A solution of 4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (730 mg, 2.31 mmol) in anhydrous DMF is added slowly to a stirred solution of 60% NaH (1108 mg, 27.72 mmol) in anhydrous DMF (20 mL) at 0° C. under N2 and stirred at rt for an hour. HOSA (1305 mg, 11.55 mmol) is added portion-wise at 0° C., stirred at 0° C. for 5 hours, poured into ice/water (350 mL) and extracted with ether (3×35 mL). The combined organic extract is washed with water (2×20 mL) and brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue is washed with heptane (3×5 mL) to afford 4-(1-Amino-5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (715 mg, 94%) as a solid. MS: 332 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.52 (d, H), 7.36 (m, H), 7.20 (s, H), 7.04 (t, H), 6.06 (s, H), 4.78 (s, 2H), 4.15(m, 2H), 3.69 (t, 2H), 2.54 (s, 2H), 1.55 (s, 9H).

Workup

  1. additionHOSA (1305 mg, 11.55 mmol) is added portion-wise at 0° C.
  2. stirringstirred at 0° C. for 5 hours
  3. extractionextracted with ether (3×35 mL)
  4. extractionThe combined organic extract
  5. washis washed with water (2×20 mL) and brine (20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washThe residue is washed with heptane (3×5 mL)

Sources & evidence

ORD record
ord-b8ef54bb46a649cda0d2dad76eb5a20d
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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