Dimethylformamide → 2-(5-Methoxy-2-methyl-1h-indol-3-yl)acetamide

HRID 381400

Reaction equation

HRID 381400 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH2:13][C:14]([OH:16])=O.CC[N:19]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[Cl-].[NH4+].CN(C=O)C>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH2:13][C:14]([NH2:19])=[O:16]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 761515-Methoxy-2-methylindole-3-acetic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 2441462-(5-Methoxy-2-methyl-1h-indol-3-yl)acetamideYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A reaction mixture containing Compound 1 (880 mg, 4.02 mmol), EDCl (1.16 g,6.04 mmol), HOBt (816 mg,6.04 mmol), DIPEA (2.8 mL, 16.08 mmol), ammonium chloride (430 mg, 8.04 mmol) in anhydrous DMF 16 mL (4 mL DMF/1 mmol) was stirred at rt for 5 hours. The reaction was diluted with water and extracted with EtOAc (3×10 mL). The combined EtOAc extracts were washed with saturated NaHCO3 (2×10 mL), water, dried (MgSO4), filtered, and the solvent concentrated in vacuo till a minimum volume of EtOAc remained. Upon cooling, the desired primary amide crystallized out as a white crystalline solid, in 64% yield. mp=146-148° C. t is noted that Shaw, “The Synthesis of Tryptamines Related to Seratonin”, Vol. 77, J. Amer. Chem. Soc., pp. 4319-4324 (1955) reported the mp=147-150° C. 1H NMR (DMSO-d6) δ 10.56 (s, 1 H, NH), 7.34 (bs, 1 H, CONH), 6.96-7.22 (m, 1 H, ArH), 6.81 (s, 1 H, ArH), 6.74 (bs, 1 H, CONH), 6.58-6.62 (m, 1 H, ArH), 3.78 (s, 3 H, CH3), 3.34 (s, 2 H, CH2), 2.29 (s, 3 H, CH3). ESI-CID 219 (MH+), m/z 187, 174, 148.

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washThe combined EtOAc extracts were washed with saturated NaHCO3 (2×10 mL), water
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationthe solvent concentrated in vacuo till a minimum volume of EtOAc
  6. temperatureUpon cooling
  7. customthe desired primary amide crystallized out as a white crystalline solid, in 64% yield
  8. customThe Synthesis of Tryptamines

Sources & evidence

ORD record
ord-9cda3f52a85642a796926de967d07843
Source dataset
uspto-grants-2001_10
Patent number
US06306890B1

Linked notes

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