Tetrahydrofuran → 2-Amino-5-(4-heptanoylaminophenyl)imidazole-1-carboxylic acid tert-butyl ester

HRID 1468569Notes

Reaction equation

HRID 1468569 reaction equation
C1COCC1.[C:6]([O:10][C:11]([N:13]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([N:24]=[N+]=[N-])=[CH:20][CH:19]=2)=[CH:16][N:15]=[C:14]1[NH2:27])=[O:12])([CH3:9])([CH3:8])[CH3:7].C(N(CC)CC)C.[C:35](Cl)(=[O:42])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>ClCCl.[Pd]>[C:6]([O:10][C:11]([N:13]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:35](=[O:42])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:20][CH:19]=2)=[CH:16][N:15]=[C:14]1[NH2:27])=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 17313Heptanoyl chlorideHCID 579314382-Amino-5-(4-azidophenyl)imidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 579314562-Amino-5-(4-heptanoylaminophenyl)imidazole-1-carboxylic acid tert-butyl esterYield 97%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of anhydrous THF (5 mL) and 10% Pd/C (0.010 g) was charged 2-amino-5-(4-azidophenyl)imidazole-1-carboxylic acid tert-butyl ester (0.100 g, 0.332 mmol). Air was removed from the system and the reaction was back flushed with hydrogen. This process was repeated three times before setting the reaction under a hydrogen balloon at atmospheric pressure and temperature for 12 h. After that time, the reaction was filtered to remove the catalyst. The filtrate was cooled to −78° C. and triethylamine (0.046 mL, 0.332 mmol) was added prior to the drop-wise addition of heptanoyl chloride (0.049 g, 0.332 mmol) diluted in anhydrous dichloromethane (0.50 mL). The reaction was stirred at −78° C. for 30 mins and then quenched with methanol (1 mL) before being concentrated under reduced pressure and purified by flash column chromatography (10-60% EtOAc/Hexanes) to obtain the title compound 2-amino-5-(4-heptanoylaminophenyl)imidazole-1-carboxylic acid tert-butyl ester (0.124 g, 97%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 10.08 (s, 1H), 8.14 (br s, 2H), 7.67 (m, 4H), 7.56 (s, 1H), 2.32 (t, 2H, J=7.5 Hz), 1.49 (m, 11H), 1.28 (br s, 6H), 0.87 (t, 2H, J=6.0 Hz); 13C NMR (75 MHz, DMSO-d6) δ 171.4, 147.5, 139.1, 126.4, 124.7, 122.2, 119.2, 119.0, 111.4, 108.4, 36.4, 31.0, 28.3, 27.4, 25.0, 21.9, 13.9; HRMS (ESI) calcd for C21H30N4O3 (M+) 386.2318. found

Workup

  1. customAir was removed from the system
  2. customthe reaction was back flushed with hydrogen
  3. customthe reaction under a hydrogen balloon at atmospheric pressure and temperature for 12 h
  4. filtrationAfter that time, the reaction was filtered
  5. customto remove the catalyst
  6. customquenched with methanol (1 mL)
  7. concentrationbefore being concentrated under reduced pressure
  8. custompurified by flash column chromatography (10-60% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-04fcd2fd424a44c183e24a436ec3a2d7
Source dataset
uspto-grants-2015_04
Patent number
US09005643B2

Reaction notes

Loading…