Chloroacetyl chloride → 3-amino-6-(2-chloro-acetyl)-4-thiophen-2-yl-6,7-dihydro-5H-1-thia-6,8-diaza-s-indacene-2-carboxylic acid amide

HRID 2375367Notes

Reaction equation

HRID 2375367 reaction equation
Cl.[NH2:2][C:3]1[C:14]2[C:6](=[N:7][C:8]3[CH2:9][NH:10][CH2:11][C:12]=3[C:13]=2[C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)[S:5][C:4]=1[C:20]([NH2:22])=[O:21].C(N(C(C)C)CC)(C)C.[Cl:32][CH2:33][C:34](Cl)=[O:35]>CN(C=O)C.C1COCC1>[NH2:2][C:3]1[C:14]2[C:6](=[N:7][C:8]3[CH2:9][N:10]([C:34](=[O:35])[CH2:33][Cl:32])[CH2:11][C:12]=3[C:13]=2[C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)[S:5][C:4]=1[C:20]([NH2:22])=[O:21]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 689136683-Amino-4-thiophen-2-yl-6,7-dihydro-5H-1-thia-6,8-diaza-s-indacene-2-carboxylic acid amide hydrochloride

Product 1

HCID 598548793-amino-6-(2-chloro-acetyl)-4-thiophen-2-yl-6,7-dihydro-5H-1-thia-6,8-diaza-s-indacene-2-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To 50 mg (0.158 mmol) of 3-amino-4-thiophen-2-yl-6,7-dihydro-5H-1-thia-6,8-diaza-s-indacene-2-carboxylic acid amide hydrochloride in 3.0 ml of DMF was added dropwise 0.32 ml of 1.0 M solution containing diisopropylethylamine (DIPEA) in THF and (0.16 mmol) of 2-chloroacetyl chloride in 1.0 ml of DMF, according to standard procedures. The resulting mixture was continuously stirred at room temperature for several hours, and the progress of the reaction was monitored by TLC. The solvent was removed under vacuum, and the residue was recrystallized from a polar solvent. Similar procedures were used for 3-amino-6-[2-(4-benzyl-cyclohexylamino)-acetyl]-4-thiophen-2-yl-6,7-dihydro-5H-1-thia-6,8-diaza-s-indacene-2-carboxylic acid amide (103) and 3-amino-6-(6-morpholin-4-yl-pyridine-3-carbonyl)-4-thiophen-2-yl-6,7-dihydro-5H-1-thia-6,8-diaza-s-indacene-2-carboxylic acid amide (105). In some cases, if the product was not recrystallized from methanol or ethanol, the reaction mixture was purified by flash column chromatography or preparative HPLC. All products were verified by NMR spectroscopy.

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was recrystallized from a polar solvent
  3. customIn some cases, if the product was not recrystallized from methanol or ethanol
  4. customthe reaction mixture was purified by flash column chromatography or preparative HPLC

Sources & evidence

ORD record
ord-0618708822ba476cb6da7445241b1780
Source dataset
uspto-grants-2008_12
Patent number
US07465742B2

Reaction notes

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