Dimethylformamide → HCID 70816926, compound

HRID 1261765Notes

Reaction equation

HRID 1261765 reaction equation
[CH3:1]N(C)C=O.O1CCCC1.C(Cl)(=O)C(Cl)=O.[CH3:17][O:18][C:19](=[O:44])[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=2[NH:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=2)=[O:29])=[CH:22][CH:21]=1>O.C1(C)C=CC=CC=1>[CH3:17][O:18][C:19](=[O:44])[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]2[C:28](=[O:29])[C:30]3[C:31](=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=3)[N:37]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[CH:1]=2)=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 65578Oxalyl chlorideHCID 70816758HCID 70816758, compound

Product 1

HCID 70816926HCID 70816926, compoundYield 9.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N,N-dimethylformamide (268 mg, 286 μL, 3.67 mmol) and tetrahydrofuran (2.94 mL) cooled to 0° C. was treated with oxalyl chloride (373 mg, 256 μL, 2.94 mmol). During the addition process, vigorous gas evolution occurred, the reaction became cloudy and a thick white precipitate formed. At this time, the ice bath was removed. The reaction mixture was stirred at 25° C. for 45 min and then was concentrated in vacuo. The resulting white paste was treated with toluene (11.8 mL) and 4-{3-[4-chloro-2-(pyridin-2-ylamino)-phenyl]-3-oxo-propyl}-benzoic acid methyl ester (290 mg, 734 μmol). This mixture was then heated to 115° C. for 5 h and then was stirred at 25° C. overnight. At this time, the reaction was diluted with water (30 mL) and extracted into methylene chloride (3×30 mL). The organics were dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (40 g column; 1-10% methanol/methylene chloride) afforded 4-(7-chloro-4-oxo-1-pyridin-2-yl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester (28.7 mg, 9.65%) as a brown solid. ES+-HRMS m/e calcd for C23H17ClN2O3 [M+H+] 405.1000. Found 405.0995; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.73 (d, J=4.7 Hz, 1H) 8.29 (s, 1H) 8.14-8.24 (m, 2H) 7.85 (d, J=8.2 Hz, 2H) 7.79 (d, J=7.9 Hz, 1H) 7.63-7.72 (m, 1H) 7.47 (d, J=8.2 Hz, 2H) 7.43 (m, 1H) 7.21 (d, J=1.7 Hz, 1H) 3.89 (s, 2H) 3.82 (s, 3H).

Workup

  1. customa thick white precipitate formed
  2. customAt this time, the ice bath was removed
  3. concentrationwas concentrated in vacuo
  4. temperatureThis mixture was then heated to 115° C. for 5 h
  5. stirringwas stirred at 25° C. overnight
  6. extractionextracted into methylene chloride (3×30 mL)
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee17e4aaff954939930acebaf162eb1d
Source dataset
uspto-grants-2013_06
Patent number
US08471027B2

Reaction notes

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