Formamide → 2-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetamide

HRID 1968734Notes

Reaction equation

[CH:1]([NH2:3])=[O:2].C(OC(=O)[CH2:8][C:9]1[C:10]([Cl:23])=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH2:19][N:20]([CH3:22])[CH3:21])[CH:15]=[CH:14]2)C.C[O-].[Na+]>CN(C)C=O.O>[Cl:23][C:10]1[C:9]([CH2:8][C:1]([NH2:3])=[O:2])=[C:18]2[C:13]([CH:14]=[CH:15][C:16]([CH2:19][N:20]([CH3:21])[CH3:22])=[N:17]2)=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 105 °C

Procedure

Formamide (118 mg, 2.62 mmol, 3.35 equiv) was added to a solution of (7-chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetic acid ethyl ester (240 mg, 0.78 mmol) in N,N-dimethylformamide (1.0 ml). The solution was heated to 105° C., and then sodium methoxide (5.4 M in MeOH, 0.14 ml, 0.78 mmol, 1.0 equiv) was added dropwise over 20 minutes. After 1 hour, the reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc and CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue via flash chromatography (gradient of CH2Cl2/MeOH 96:4 to 60:40) afforded the title compound (161 mg, 74%) as a white solid. 1H NMR (400 MHz, d6-DMSO): δ=8.35 (d, J=8.9 Hz, 1H), 7.89 (d, J=9.2 Hz, 1H), 7.63 (d, J=9.2 Hz, 1H), 7.60 (d, J=8.9 Hz, 1H), 7.41 (br s, 1H), 6.88 (br s, 1H), 4.26 (s, 2H), 3.69 (s, 2H), 2.21 (s, 6H). MS (ES+): 278.3 (M+H)+.

Workup

temperaturethe reaction mixture was cooled to room temperature
extractionextracted with EtOAc and CH2Cl2
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the residue via flash chromatography (gradient of CH2Cl2/MeOH 96:4 to 60:40)

Sources & evidence

ORD record: ord-f9f9130e9f94486a9f789ae663f6963e
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426440B2

Reaction notes

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