Toluene → heptanoic acid [4-(2-amino-3H-imidazol-4-yl)phenyl]amide hydrochloride

HRID 1468570Notes

Reaction equation

HRID 1468570 reaction equation
C(OC([N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:15][CH:14]=2)=[CH:11][N:10]=[C:9]1[NH2:28])=O)(C)(C)C.FC(F)(F)C(O)=O.C1(C)C=CC=CC=1.[Cl:43]CCl>>[ClH:43].[NH2:28][C:9]1[NH:8][C:12]([C:13]2[CH:14]=[CH:15][C:16]([NH:19][C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:17][CH:18]=2)=[CH:11][N:10]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 579314562-Amino-5-(4-heptanoylaminophenyl)imidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 46890039heptanoic acid [4-(2-amino-3H-imidazol-4-yl)phenyl]amide hydrochlorideYield 97%

Conditions

Temperature
0 °C

Procedure

2-amino-5-(4-heptanoylaminophenyl)imidazole-1-carboxylic acid tert-butyl ester (0.089 g, 0.230 mmol) was dissolved in anhydrous dichloromethane (5 mL) and cooled to 0° C. Trifluoroacetic acid (0.50 mL) was added drop-wise while the reaction continued to stir at 0° C. Upon completion, the reaction was allowed to warm to room temperature over the course of 12 h. Toluene (2 mL) was added and the reaction was evaporated to dryness. The crude TFA salt was then dissolved in dichloromethane (3 mL) and a 2M solution of HCl in diethyl ether (0.10 mL) was added. The solution was again concentrated under reduced pressure and the resulting product triturated with cold diethyl ether (5 mL) to afford 0.072 g (97%) of the desired compound heptanoic acid [4-(2-amino-3H-imidazol-4-yl)phenyl]amide in its corresponding hydrochloride form as a yellow amorphous solid: 1H NMR (300 MHz, DMSO-d6) δ 12.80 (s, 1H), 12.05 (s, 1H), 10.08 (s, 1H), 7.67 (d, 2H, J=8.1 Hz), 7.59 (d, 2H, J=8.1 Hz), 7.43 (br s, 2H), 7.27 (s, 1H), 2.31 (t, 2H, J=6.8 Hz), 1.58 (m, 2H), 1.27 (m, 6H), 0.86 (t, 3H, J=5.7 Hz); 13C NMR (75 MHz, DMSO-d6) δ 172.1, 148.2, 139.8, 127.1, 125.4, 123.0, 119.9, 109.1, 37.1, 31.7, 29.0, 25.7, 22.7, 14.6; HRMS (ESI) calcd for C16H22N4O (M+) 286.1794. found 286.1788.

Workup

  1. temperatureto warm to room temperature over the course of 12 h
  2. customthe reaction was evaporated to dryness
  3. dissolutionThe crude TFA salt was then dissolved in dichloromethane (3 mL)
  4. additiona 2M solution of HCl in diethyl ether (0.10 mL) was added
  5. concentrationThe solution was again concentrated under reduced pressure
  6. customthe resulting product triturated with cold diethyl ether (5 mL)

Sources & evidence

ORD record
ord-b37df41ba3a8431296937b9ba8620105
Source dataset
uspto-grants-2015_04
Patent number
US09005643B2

Reaction notes

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