Triethylamine → 5-Chloro-N-{2-[1-(cyanomethyl)-4-piperidinyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-2-thiophenecarboxamide

HRID 457750Notes

Reaction equation

HRID 457750 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[C:12](=[O:26])[N:13]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[C:14]3=[O:19])=[O:8])=[CH:4][CH:3]=1.Br[CH2:28][C:29]#[N:30].C(N(CC)CC)C>CN(C=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[C:12](=[O:26])[N:13]([CH:20]2[CH2:25][CH2:24][N:23]([CH2:28][C:29]#[N:30])[CH2:22][CH2:21]2)[C:14]3=[O:19])=[O:8])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11534BromoacetonitrileHCID 120748935-chloro-N-[1,3-dioxo-2-(4-piperidinyl)-2,3-dihydro-1H-isoindol-4-yl]-2-thiophenecarboxamide

Product 1

HCID 120732455-Chloro-N-{2-[1-(cyanomethyl)-4-piperidinyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 100 mg (0.26 mmol) of 5-chloro-N-[1,3-dioxo-2-(4-piperidinyl)-2,3-dihydro-1H-isoindol-4-yl]-2-thiophenecarboxamide, 0.022 ml (0.31 mmol) of α-bromoacetonitrile and 0.072 ml (0.51 mmol) of triethylamine in 2.5 ml of DMF are stirred at room temperature overnight. The mixture is concentrated and the residue is taken up in dichloromethane, washed with sodium bicarbonate solution, dried over magnesium sulfate and concentrated. The product is crystallized with ether, filtered off with suction and dried under high vacuum. Alternatively, the product can be purified by chromatography on silica gel (dichloromethane/methanol mixtures).

Workup

  1. concentrationThe mixture is concentrated
  2. washwashed with sodium bicarbonate solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe product is crystallized with ether
  6. filtrationfiltered off with suction
  7. customdried under high vacuum
  8. customAlternatively, the product can be purified by chromatography on silica gel (dichloromethane/methanol mixtures)

Sources & evidence

ORD record
ord-d20c3ec95666456e8ac0e20e68201e11
Source dataset
uspto-grants-2007_03
Patent number
US07189738B2

Reaction notes

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