Sodium hydride → HCID 57155986, compound

HRID 1599044Notes

Reaction equation

HRID 1599044 reaction equation
[H-].[Na+].[C:3]1([CH:9]([O:32][CH2:33][C:34]2[CH:39]=[CH:38]C=[CH:36][CH:35]=2)[C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH:19]([N:22]4[CH2:30][C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[C:23]4=[O:31])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N:40]1C=CC(CCl)=CC=1>CN(C=O)C>[N:40]1[CH:36]=[CH:35][C:34]([CH2:33][O:32][CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH:19]([N:22]4[CH2:30][C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[C:23]4=[O:31])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 745714-(Chloromethyl)pyridineHCID 18784744HCID 18784744, compound

Product 1

HCID 57155986HCID 57155986, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (55.3 mg, 1.38 mmol) in DMF (5 mL) at 0° C. was added dropwise a solution of Example 293 Part A compound (500 mg, 1.26 mmol) in DMF (8 mL). The reaction was stirred at 0° C. for 30 min. A solution of 4-picolyl chloride (175 mg, 1.38 mmol) in DMF (1 mL) was added dropwise to the reaction at 0° C. The reaction was stirred at 0° C. for 1 h then warmed to RT overnight. The reaction was quenched with saturated ammonium chloride solution (2 mL). Ethyl acetate (200 mL) was added to the reaction, and the organic layer was washed with water (2×100 mL), brine (2×100 mL) and dried over MgSO4. Purification was performed by flash chromatography on silica gel (100 g), loaded and eluted with 70% EtOAc in hexane. Pure fractions were combined and evaporated to give title compound (320 mg, 52%) as a white solid.

Workup

  1. stirringThe reaction was stirred at 0° C. for 1 h
  2. temperaturethen warmed to RT overnight
  3. customThe reaction was quenched with saturated ammonium chloride solution (2 mL)
  4. additionEthyl acetate (200 mL) was added to the reaction
  5. washthe organic layer was washed with water (2×100 mL), brine (2×100 mL)
  6. dry with materialdried over MgSO4
  7. customPurification
  8. washeluted with 70% EtOAc in hexane
  9. customevaporated

Sources & evidence

ORD record
ord-ec8536515e504a818555cf2f13675b3f
Source dataset
uspto-grants-1998_04
Patent number
US05739135

Reaction notes

Loading…