Sodium hydride → HCID 19601663, compound

HRID 610651Notes

Reaction equation

HRID 610651 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]([C:18]([NH:20][CH3:21])=[O:19])[N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[F:24][CH2:25][CH2:26][CH2:27]Br>CN(C=O)C>[I:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]([C:18]([N:20]([CH3:21])[CH2:27][CH2:26][CH2:25][F:24])=[O:19])[N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67699Propane, 1-bromo-3-fluoro-HCID 19601665HCID 19601665, compound

Product 1

HCID 19601663HCID 19601663, compoundYield 40.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-iodophenyl)-N-methyl-3-isoquinolinecarboxamide (25 mg, 0.06 mmol) in DMF (4 mL) was added 60% NaH (10 mg, 0.25 mmol) in one portion. The mixture was stirred under Ar at room temperature for 30 min. Then, 3-fluoropropyl bromide (20 μl, 0.27 mmol) was added. After stirring at room temperature for overnight, the mixture was quenched by adding H2O (5 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried (MgSO4), filtered. The filtrate was concentrated in vacuo. The residue was chromatographed (SiO2, 30% ethyl acetate/hexane, 0.035% Et3N), thereby affording a semisolid (11 mg, 40%). 1H NMR (CDCl3) d 2.01-2.22 (m, 2 H, CH2), 3.15, 3.17 (two s, total 3 H, N-methyl), 3.60-3.76 (m, 2 H, N--CH2), 4.22-4.76 (qt, J=77.7, 47.1, 5.7 Hz, 2 H, CH2F), 7.36-7.47 (m, 1 H, aromatic), 7.50-7.81 (m, 4 H, aromatic), 7.82-7.99 (m, 2 H, aromatic), 7.83-8.16 (m, 2 H, aromatic). HRMS calcd. for C20H18FIN2O: 448.0448. Found: 448.0435.

Workup

  1. stirringAfter stirring at room temperature for overnight
  2. customthe mixture was quenched
  3. additionby adding H2O (5 mL)
  4. extractionThe mixture was extracted with CH2Cl2 (3×15 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe residue was chromatographed (SiO2, 30% ethyl acetate/hexane, 0.035% Et3N)

Sources & evidence

ORD record
ord-1d1a693db1184be5a7bf586e6b9943e8
Source dataset
uspto-grants-1999_12
Patent number
US05998624

Reaction notes

Loading…