Triethylamine → N-(4-Isopropylbenzenesulfonyl)-alpha-[2-n-propyl-4-[[(2-pyridylmethyl)amino]carbonyl]phenoxy]-3,4-methylenedioxyphenylacetamide

HRID 744190Notes

Reaction equation

HRID 744190 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14](=[O:38])[CH:15]([C:29]2[CH:34]=[CH:33][C:32]3[O:35][CH2:36][O:37][C:31]=3[CH:30]=2)[O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([OH:25])=O)=[CH:19][C:18]=2[CH2:26][CH2:27][CH3:28])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=1.C(N(CC)CC)C>C(#N)C.C1COCC1>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14](=[O:38])[CH:15]([C:29]2[CH:34]=[CH:33][C:32]3[O:35][CH2:36][O:37][C:31]=3[CH:30]=2)[O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([NH:51][CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=3)=[O:25])=[CH:19][C:18]=2[CH2:26][CH2:27][CH3:28])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 195092-PyridinemethanamineHCID 682631,1'-CarbonyldiimidazoleHCID 98944604-[1-(1,3-Benzodioxol-5-yl)-2-oxo-2-[(4-propan-2-ylphenyl)sulfonylamino]ethoxy]-3-propylbenzoic acid

Product 1

HCID 15383765N-(4-Isopropylbenzenesulfonyl)-alpha-[2-n-propyl-4-[[(2-pyridylmethyl)amino]carbonyl]phenoxy]-3,4-methylenedioxyphenylacetamideYield 82%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 200 mg (0.371 mmol) of N-(4-isopropylbenzenesulfonyl)-α-(4-carboxy-2-n-propylphenoxy)-3,4-methylenedioxyphenylacetamide (from Step D) in 2 mL of acetonitrile and 1 mL of dry THF was added 72.2 mg (0.445 mmol) of 1,1'-carbonyldiimidazole. The solution was stirred under N2 at 60° C. for 2 hours. Then 45.9 μL (48.1 mg; 0.445 mmol) of 2-(aminomethyl)pyridine was added, followed by 129 μL (93.7 mg; 0.928 mmol) of triethylamine. The solution was stirred overnight at 60° C. The cooled reaction mixture was quenched by addition of 5% citric acid solution (aqueous) and extracted twice with EtOAc. The combined organic extracts were washed twice with H2O, then with brine, dried over Na2SO4, and filtered. The filtrate was concentrated, and the residue was flash chromatographed (gradient elution with 1-6% MeOH in CH2Cl2) to give 191 mg (82%) of the title compound as a cream-colored solid, mp 168°-170° C.; homogeneous by TLC in 95:5 CH2Cl2 -MeOH. ESI mass spectrum m/e 630 (M+H)+.

Workup

  1. stirringThe solution was stirred overnight at 60° C
  2. customThe cooled reaction mixture
  3. customwas quenched by addition of 5% citric acid solution (aqueous)
  4. extractionextracted twice with EtOAc
  5. washThe combined organic extracts were washed twice with H2O
  6. dry with materialwith brine, dried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customchromatographed
  10. wash(gradient elution with 1-6% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-ebf2174ce2ba4becb44aad12979a3a80
Source dataset
uspto-grants-1996_09
Patent number
US05559135

Reaction notes

Loading…