Dimethylformamide → 3-[7-(pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester

HRID 2089533Notes

Reaction equation

HRID 2089533 reaction equation
[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19](Br)[CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2].[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.CN([CH:31]=[O:32])C>>[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:31]([N:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:32])[CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 31268PyrrolidineHCID 591994563-(7-bromo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

Product 1

HCID 591994453-[7-(pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester

Conditions

Temperature
100 °C

Procedure

3-[7-(Pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester and 3-[7-(dimethylcarbamoyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester can be obtained from the reaction mixture resulting from this procedure. A pressure tube fitted with a septum is charged with 3-(7-bromo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester, which can be prepared as described in Example 5, (0.304 g, 0.836 mmol), pyrrolidine (0.298 g, 4.184 mmol), (bis-triphenylphosphine)palladium dichloride (0.029 g, 0.418 mmol), and DMF (4 mL). Carbon monoxide is bubbled through the solution for 15 min, and then the septum is replaced with a screw cap and the mixture is heated to 100° C. overnight. The reaction is cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic phase is dried over sodium sulfate, filtered, and concentrated. The resulting residue is purified by silica gel chromatography (dichloromethane-methanol mixtures) to give 3-[7-(pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 382.2 (M+H)+; 1H NMR (400 MHz, MeOD) δ ppm 1.37 (d, J=6.3 Hz, 3 H), 1.39 (d, J=6.3 Hz, 3 H), 1.85-2.01 (m, 6 H), 2.28-2.33 (m, 2 H), 2.90-2.98 (m, 1 H), 3.09 (dt, J=17.4, 6.3 Hz, 1 H), 3.27-3.33 (m, 1 H), 3.38-3.42 (m, 1 H), 3.56 (t, J=6.9 Hz, 2 H), 5.21 (sept, J=6.3 Hz, 1 H), 6.37 (t, J=5.9 Hz, 1 H), 7.05 (br. s, 1 H), 7.36 (d, J=7.8 Hz, 1 H), 7.45 (dd, J=7.8, 1.5 Hz, 1 H), 7.56 (s, 1 H), 7.76 (s, 1 H); and

Workup

  1. customresulting from this procedure
  2. customA pressure tube fitted with a septum
  3. customcan be prepared
  4. customCarbon monoxide is bubbled through the solution for 15 min
  5. customcap
  6. temperatureThe reaction is cooled to room temperature
  7. additiondiluted with water
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic phase is dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue is purified by silica gel chromatography (dichloromethane-methanol mixtures)

Sources & evidence

ORD record
ord-f91398f63b3544d48f87a855351a9a20
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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