Sodium hydride → HCID 19601655, compound

HRID 610655Notes

Reaction equation

HRID 610655 reaction equation
[CH2:1]([Sn:5]([CH2:30][CH2:31][CH2:32][CH3:33])([CH2:26][CH2:27][CH2:28][CH3:29])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]([C:22]([NH:24][CH3:25])=[O:23])[N:13]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[F:36][CH2:37][CH2:38][CH2:39]Br>CN(C=O)C>[CH2:30]([Sn:5]([CH2:1][CH2:2][CH2:3][CH3:4])([CH2:26][CH2:27][CH2:28][CH3:29])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]([C:22]([N:24]([CH3:25])[CH2:39][CH2:38][CH2:37][F:36])=[O:23])[N:13]=1)[CH2:31][CH2:32][CH3:33]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67699Propane, 1-bromo-3-fluoro-HCID 19601680HCID 19601680, compound

Product 1

HCID 19601655HCID 19601655, compoundYield 25.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(2-tributylstannylphenyl)-N-methyl-3-isoquinoline-carboxamide (105 mg, 0.19 mmol) in DMF (5 mL) was added 60% NaH (65 mg, 1.61 mmol) in one portion. The mixture was stirred under Ar at room temperature for 40 min. Then, 3-fluoropropyl bromide (124 μl, 1.67 mmol) was added. After stirring under Ar at room temperature for 24 h, the mixture was quenched by adding H2O (9 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, 5-10% ethyl acetate/hexane, 0.1% Et3N), thereby affording an oil (29.3 mg, 25%), and starting material (62.5 mg). 1H NMR (CDCl3) d 0.32-0.68 (m, 6 H, SnCH2), 0.70 (t, J=7.2 Hz, 9 H, CH3), 0.95-1.32 (m, 12 H, CH2CH2), 2.15-2.28 (m, 2 H, CH2), 3.13 (d, J=11.1 Hz, 3 H, N-methyl), 3.58-3.85 (m, 2 H, N--CH2), 4.48 (qt, J=123.9, 47.4, 5.7 Hz, 2 H, CH2F), 7.42-7.62 (m, 4 H, aromatic), 7.65-7.80 (m, 2 H, aromatic), 7.91-8.15 (m, 3 H, aromatic). HRFABMS Calcd. for C32H46FN2O12OSn: 613.2599. Found: 613.2619.

Workup

  1. stirringAfter stirring under Ar at room temperature for 24 h
  2. customthe mixture was quenched
  3. additionby adding H2O (9 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, 5-10% ethyl acetate/hexane, 0.1% Et3N)

Sources & evidence

ORD record
ord-241f21234c204de6b81129d89b1abb89
Source dataset
uspto-grants-1999_12
Patent number
US05998624

Reaction notes

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