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

HRID 505221Notes

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 chromatrography (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 chromatrography (gradient of CH2Cl2/MeOH 96:4 to 60:40)

Sources & evidence

ORD record: ord-4f389a302ec94a508aa284a254b2a58b
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07781438B2

Reaction notes

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