Acetic Acid → 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester

HRID 627028Notes

Reaction equation

Cl.[CH3:2][NH:3][CH3:4].C=O.[NH:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[CH:9]=[C:8]1[C:16]([O:18][CH2:19][CH3:20])=[O:17].[C:21](O)(=O)C>C(O)C>[CH2:19]([O:18][C:16]([C:8]1[NH:7][C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[C:9]=1[CH2:2][N:3]([CH3:21])[CH3:4])=[O:17])[CH3:20]

Participants

Conditions

Temperature: 85 °C

Procedure

In a 50 mL round-bottomed flask, dimethylamine hydrochloride (4.91 g, 60.3 mmol, Eq: 6) was added to 37% aqueous formaldehyde (4.49 mL, 60.3 mmol, Eq: 6). Ethyl 1H-pyrrolo[2,3-b]pyridine-2-carboxylate (1.91 g, 10.0 mmol, Eq: 1.00) in ethanol (50 mL) was added followed by acetic acid (5.00 mL, 87.3 mmol, Eq: 8.7). The reaction mixture was heated to 85° C. and stirred over the weekend. The crude reaction mixture was filtered through a pad of Celite, concentrated in vacuo to ˜20% of its original volume, water (100 mL) was added, and this was then washed with DCM (50 mL). The aqueous layer was cooled, basified to pH 11 through the addition of 3 M aqueous NaOH and extracted with DCM. The organic layers were dried over Na2SO4 and concentrated in vacuo to give 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester as light yellow solid (1.9 g), m/z=248 (M+H).

Workup

customThe crude reaction mixture
filtrationwas filtered through a pad of Celite
concentrationconcentrated in vacuo to ˜20% of its original volume, water (100 mL)
additionwas added
washthis was then washed with DCM (50 mL)
temperatureThe aqueous layer was cooled
additionbasified to pH 11 through the addition of 3 M aqueous NaOH
extractionextracted with DCM
dry with materialThe organic layers were dried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-5542dbd42dab4665a4149884cd05b54f
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309248B2

Reaction notes

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