Sodium hydride → HCID 15870543, compound

HRID 610649Notes

Reaction equation

HRID 610649 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([C:18]([NH:20][CH3:21])=[O:19])[N:9]=1.[H-].[Na+].[F:24][CH2:25][CH2:26][CH2:27]Br>CN(C=O)C>[I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([C:18]([N:20]([CH3:21])[CH2:27][CH2:26][CH2:25][F:24])=[O:19])[N:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67699Propane, 1-bromo-3-fluoro-HCID 15870542HCID 15870542, compound

Product 1

HCID 15870543HCID 15870543, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(2-iodophenyl)-N-methyl-3-isoquinolinecarboxamide (22 mg, 0.06 mmol) in DMF (2 mL) was added 60% NaH (12 mg, 0.30 mmol) in one portion. The mixture was stirred under Ar at room temperature for 40 min. Then, 3-fluoropropyl bromide (22 ul, 0.30 mmol) was added. After stirring under Ar at room temperature for 24 h, the mixture was quenched by adding H2O (7 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 (6 mg, 23%), and starting material (17.7 mg). 1H NMR (CDCl3) d 1.96-2.22 (m, 2 H, CH2), 3.16, 3.20 (two s, total 3 H, N-methyl), 3.59-3.85 (m, 2 H, N--CH2), 4.47 (qt, J=79.8, 47.1, 6 Hz, 2 H, CH2F), 7.21 (dt, J=7.5, 0.9 Hz, 1 H, aromatic), 7.36 (dd, J=7.5, 1.5 Hz, 1 H, aromatic), 7.51 (t, J=7.2 Hz, 1 H, aromatic), 7.56 (d, J=3.9 Hz, 2 H, aromatic), 7.69-7.81 (m, 1 H, aromatic), 7.99 (t, J=7.8 Hz, 1 H, aromatic), 8.11, 8.18 (two s, total 1 H, aromatic). HRMS calcd. for C20H18FIN2O: 448.0448. Found: 448.0456.

Workup

  1. stirringAfter stirring under Ar at room temperature for 24 h
  2. customthe mixture was quenched
  3. additionby adding H2O (7 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-1056780ec7044a49b95f43b3193887b4
Source dataset
uspto-grants-1999_12
Patent number
US05998624

Reaction notes

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