Trifluoroacetic acid → 2-(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-acetamide

HRID 402883Notes

Reaction equation

HRID 402883 reaction equation
C([O:5][C:6](=O)[CH2:7][C:8]1[N:16]2[C:11]([CH:12]=[CH:13][C:14]([CH2:17][N:18]([CH3:20])[CH3:19])=[CH:15]2)=[CH:10][C:9]=1[CH3:21])(C)(C)C.FC(F)(F)C(O)=O.C(C1NC=CN=1)(C1[NH:33]C=CN=1)=O>C(Cl)Cl>[CH3:19][N:18]([CH2:17][C:14]1[CH:13]=[CH:12][C:11]2[N:16]([C:8]([CH2:7][C:6]([NH2:33])=[O:5])=[C:9]([CH3:21])[CH:10]=2)[CH:15]=1)[CH3:20]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 68712027(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-acetic acid tert-butyl ester

Product 1

HCID 591920212-(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-acetamideYield 91.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-acetic acid tert-butyl ester (122 mg, 0.40 mmol) is dissolved in CH2Cl2 (10 ml) containing 5% of trifluoroacetic acid. The mixture is stirred for 14 hours at room temperature and then concentrated in vacuo. The residue is azeotroped twice with toluene, dissolved in N,N-dimethylformamide (2.0 ml) and treated with carbonyl diimidazole (76 mg, 0.44 mmol, 1.1 equiv). After 1 hour at room temperature, the volatiles are removed in vacuo, and the activated acid is taken up in concentrated aqueous ammonia (10 ml). The mixture is stirred for 30 minutes at room temperature and then concentrated in vacuo. The residue is purified via flash chromatography (CH2Cl2/MeOH 7:1) to afford the title compound (90 mg, 91%). 1H NMR (400 MHz, d6-DMSO): δ=7.31 (s, 1H), 7.27 (s, 1H), 6.75 (s, 1H), 6.61 (dd, J=9.3/1.5 Hz, 1H), 4.06 (s, 2H), 3.38 (s, 2H), 2.66 (s, 6H), 2.13 (s, 3H). MS (ES+): 246 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue is azeotroped twice with toluene
  3. dissolutiondissolved in N,N-dimethylformamide (2.0 ml)
  4. waitAfter 1 hour at room temperature
  5. customthe volatiles are removed in vacuo
  6. stirringThe mixture is stirred for 30 minutes at room temperature
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified via flash chromatography (CH2Cl2/MeOH 7:1)

Sources & evidence

ORD record
ord-22a34c66d1ce4dea8d79043b3af412ee
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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