Sodium hydride → HCID 11705660, compound

HRID 2059609Notes

Reaction equation

HRID 2059609 reaction equation
[CH3:1][O:2][C:3]1[CH:30]=[CH:29][C:6]2[C:7]([C:15]([C:17]3[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([O:27][CH3:28])[CH:18]=3)=[O:16])=[C:8]([C:10]3[CH:11]=[N:12][NH:13][CH:14]=3)[O:9][C:5]=2[CH:4]=1.[H-].[Na+].Cl.Cl[CH2:35][CH2:36][N:37]([CH3:39])[CH3:38]>CS(C)=O>[CH3:38][N:37]([CH3:39])[CH2:36][CH2:35][N:13]1[CH:14]=[C:10]([C:8]2[O:9][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[CH:30]=[CH:29][C:6]=3[C:7]=2[C:15]([C:17]2[CH:18]=[C:19]([O:27][CH3:28])[C:20]([O:25][CH3:26])=[C:21]([O:23][CH3:24])[CH:22]=2)=[O:16])[CH:11]=[N:12]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 11661458HCID 11661458, compound

Product 1

HCID 11705660HCID 11705660, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of [6-Methoxy-2-(1H-pyrazol-4-yl)-benzofuran-3-yl]-(3,4,5-trimethoxyphenyl)-methanone (45 mg, 0.11 mmol) in dry DMSO (1.5 mL) was added sodium hydride (60% dispersion in mineral oil, 13 mg, 0.33 mmol) and the reaction was stirred at room temperature for 20 minutes. After this time the resulting yellow suspension was treated with 2-chloroethyl-dimethylamine hydrogen chloride (24 mg, 0.17 mmol) and heated to 35-40° C. for 5 h. The reaction was quenched with water (15 mL) and ethyl acetate (20 mL) and the aqueous layer was washed with further portions of ethyl acetate (2×10 mL). The combined organic layers were dried over magnesium sulphate and the solvent was removed under vacuum. The crude residue was purified by flash chromatography (alumina activated with 1.2% water, sequential elution—1:1 DCM:hexane, 9:1 DCM:ethyl acetate) to afford the product as a yellow resinous gum (23 mg, 44% yield). 1H-NMR (CDCl3) δ 8.17 (s, 1H), 8.00 (s, 1H), 7.12 (s, 2H), 7.11 (d, J=8.7 Hz, 1H), 7.03 (d, J=2.2 Hz, 1H), 6.79 (dd, J=8.7, 2.2 Hz, 1H), 4.23 (t, J=6.7 Hz, 2H), 3.92 (s, 3H), 3.85 (s, 3H), 3.77 (s, 6H), 2.78 (t, J=6.7 Hz, 2H), 2.27 (s, 6H). 13C-NMR (CDCl3) δ 190.3, 158.1, 153.6, 152.9, 142.2, 139.0, 133.7, 130.4, 121.7, 120.9, 113.7, 112.5, 112.2, 111.5, 106.9, 95.5, 61.0, 58.7, 56.1, 55.7, 50.4, 45.4.

Workup

  1. temperatureheated to 35-40° C. for 5 h
  2. customThe reaction was quenched with water (15 mL) and ethyl acetate (20 mL)
  3. washthe aqueous layer was washed with further portions of ethyl acetate (2×10 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulphate
  5. customthe solvent was removed under vacuum
  6. customThe crude residue was purified by flash chromatography (alumina activated with 1.2% water, sequential elution—1:1 DCM:hexane, 9:1 DCM:ethyl acetate)

Sources & evidence

ORD record
ord-76712bc53861485cbf15cbf91666db63
Source dataset
uspto-grants-2012_10
Patent number
US08278290B2

Reaction notes

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