Ethyl Bromide → Ethyl-[2-(5-phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-amine

HRID 29106Notes

Reaction equation

HRID 29106 reaction equation
Cl.[C:2]1([C:8]#[C:9][C:10]2[S:14][C:13]([C:15]3[N:16]=[C:17]4[CH:22]=[N:21][CH:20]=[CH:19][N:18]4[C:23]=3[NH2:24])=[CH:12][CH:11]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:27](Br)[CH3:28].CC(=O)OCC.C(Cl)Cl>CN(C=O)C>[CH2:27]([NH:24][C:23]1[N:18]2[CH:19]=[CH:20][N:21]=[CH:22][C:17]2=[N:16][C:15]=1[C:13]1[S:14][C:10]([C:9]#[C:8][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:11][CH:12]=1)[CH3:28]

Participants

6

Reactant 4

HCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 21226138Dichloromethane ethylacetateHCID 693193602-(5-Phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-ylamine hydrochloride

Product 1

HCID 11573751Ethyl-[2-(5-phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-amineYield 92.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

395 mg (1.25 mmol) of 2-(5-phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-ylamine hydrochloride (Example 83) were dissolved in DMF (8 ml). After addition of 100 mg (2.5 mmol) of sodium hydride (60% dispersion in mineral oil), the mixture was stirred at RT for 1 h. A solution of 74 μl (0.8 mmol) of ethyl bromide in DMF (2 ml) was then added dropwise. The reaction solution was stirred at RT for 16 h, quenched with water (10 ml) and extracted with EA (2×50 ml). The combined organic phases were dried over MgSO4, filtered and evaporated under a vacuum. 253 mg (0.74 mmol, 58% of theoretical) of ethyl-[2-(5-phenylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyrazin-3-yl]-amine were obtained by means of column chromatography (silica gel, EA/DCM 4:1).

Workup

  1. stirringThe reaction solution was stirred at RT for 16 h
  2. customquenched with water (10 ml)
  3. extractionextracted with EA (2×50 ml)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. filtrationfiltered
  6. customevaporated under a vacuum

Sources & evidence

ORD record
ord-bce83af9c2454030b10934d6475f3838
Source dataset
uspto-grants-2008_09
Patent number
US07420056B2

Reaction notes

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