Acetic Acid → HCID 59352972, compound

HRID 1914722Notes

Reaction equation

HRID 1914722 reaction equation
Cl[C:2]1[C:3]([NH:12][S:13]([C:16]2[N:17]=[CH:18][N:19]([CH3:21])[CH:20]=2)(=[O:15])=[O:14])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C(OC([N:29]1[CH2:34][CH2:33][CH:32]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][C:37]=2[NH2:44])[CH2:31][CH2:30]1)=O)(C)(C)C.CCO.CC(O)=O>O>[CH3:43][O:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][CH:32]2[CH2:33][CH2:34][NH:29][CH2:30][CH2:31]2)=[C:37]([NH:44][C:2]2[C:3]([NH:12][S:13]([C:16]3[N:17]=[CH:18][N:19]([CH3:21])[CH:20]=3)(=[O:15])=[O:14])=[N:4][C:5]3[C:10]([N:11]=2)=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:38]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 702EthanolHCID 57625373HCID 57625373, compoundHCID 59353087HCID 59353087, compound

Product 1

HCID 59352972HCID 59352972, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

N-(3-chloroquinoxalin-2-yl)-1-methyl-1H-imidazole-4-sulfonamide (1 g; 3.1 mmol; 1 eq) and 4-(2-amino-4-methoxy-benzyl)-piperidine-1-carboxylic acid tert-butyl ester (1.1 g; 3.4 mmol; 1.1 eq) are suspended in water (12.5 mL) and EtOH (12.5 mL) then AcOH (2.5 mL) is added. The resulting suspension is heated up to 90° C. for 3 days. Boc deprotection occurs during the reaction. The solvents are evaporated under reduced pressure and the resulting oily brown residue is taken up in water. An excess triethylamine is added until pH=8 to trap the HCl formed during the reaction. The precipitate is filtered off then washed thoroughly with water until neutral. It is dried under vacuum at 40° C. for 2 days, affording 544 mg (35%) of the title compound as a grey solid. 1H NMR (DMSO-d6) δ 9.35 (s, 1H), 8.70 (d, J=2.4 Hz, 1H), 7.69 (s, 1H), 7.50-7.30 (m, 3H), 7.35-6.97 (m, 3H), 6.48 (dd, J=8.3, 2.7 Hz, 1H), 3.89 (s, 2H), 3.78 (s, 3H), 3.63 (s, 3H), 3.45-3.15 (m, 2H), 2.97-2.78 (m, 2H), 2.65-2.53 (m, 2H), 2.05-1.80 (m, 2H), 1.56-1.32 (m, 2H). HPLC (max plot) 89%; Rt 3.08 min. LC/MS: (ES+) 508.1, (ES−) 506.1.

Workup

  1. customBoc deprotection occurs during the reaction
  2. customThe solvents are evaporated under reduced pressure
  3. additionAn excess triethylamine is added until pH=8 to trap the HCl
  4. customformed during the reaction
  5. filtrationThe precipitate is filtered off
  6. washthen washed thoroughly with water until neutral
  7. customIt is dried under vacuum at 40° C. for 2 days

Sources & evidence

ORD record
ord-8fb15243128f43d0b5fbbea587f1c68f
Source dataset
uspto-grants-2013_12
Patent number
US08614215B2

Reaction notes

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