2,6-Lutidine → 4-tert-butyl-N-[5-chloro-2-(4-methyl-5-piperidin-4-yl-4H-[1,2,4]triazol-3-yl)-pyridin-3-yl]-benzenesulfonamide

HRID 2094212Notes

Reaction equation

HRID 2094212 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=O)[NH:18][CH3:19])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:23].N1C(C)=CC=CC=1C.[C:34]([C:38]1[CH:43]=[CH:42][C:41]([S:44]([NH:47][C:48]2[C:49]([C:55]([NH:57][NH2:58])=O)=[N:50][C:51](Cl)=[CH:52][CH:53]=2)(=[O:46])=[O:45])=[CH:40][CH:39]=1)([CH3:37])([CH3:36])[CH3:35].CCN(C(C)C)C(C)C>O1CCOCC1.CC#N>[C:34]([C:38]1[CH:39]=[CH:40][C:41]([S:44]([NH:47][C:48]2[C:49]([C:55]3[N:18]([CH3:19])[C:17]([CH:14]4[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]4)=[N:58][N:57]=3)=[N:50][CH:51]=[C:52]([Cl:23])[CH:53]=2)(=[O:45])=[O:46])=[CH:42][CH:43]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 5

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 59216825Benzyl 4-(N-methylcarbamoyl)piperidine-1-carboxylateHCID 866183534-tert-butyl-N-(6-chloro-2-hydrazinocarbonyl-pyridin-3-yl)-benzenesulfonamide

Product 1

HCID 248044394-tert-butyl-N-[5-chloro-2-(4-methyl-5-piperidin-4-yl-4H-[1,2,4]triazol-3-yl)-pyridin-3-yl]-benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

A 25 mL scintillation vial was charged with 4-methylcarbamoyl-piperidine-1-carboxylic acid benzyl ester (138 mg, 0.5 mmol), POCl3 (0.095 mL, 1.0 mmol), 2,6-lutidine (130 mg, 1.25 mmol), and CH3CN (1.5 mL). The vial was sealed, heated to 40° C., and stirred for four hours. The volatiles were then evacuated in vacuo and to the resultant residue was added 4-tert-butyl-N-(6-chloro-2-hydrazinocarbonyl-pyridin-3-yl)-benzenesulfonamide (193 mg, 0.5 mmol), DIPEA (0.5 mL), and dioxane (1.0 mL). The vial was sealed, heated to 130° C., and stirred for two hours. The volatiles were then removed in vacuo and to the residue was added 3 mL of 33% hydrobromic acid in acetic acid. The vial was sealed and stirred for 3 h. The volatiles were then evacuated in vacuo and the residue was purified via preparatory HPLC to afford 4-tert-butyl-N-[5-chloro-2-(4-methyl-5-piperidin-4-yl-4H-[1,2,4]triazol-3-yl)-pyridin-3-yl]-benzenesulfonamide as a white powder: MS (ES) M+H expected 489.2. found 488.5.

Workup

  1. customThe vial was sealed
  2. customThe volatiles were then evacuated in vacuo and to the resultant residue
  3. customThe vial was sealed
  4. temperatureheated to 130° C.
  5. stirringstirred for two hours
  6. customThe volatiles were then removed in vacuo and to the residue
  7. additionwas added 3 mL of 33% hydrobromic acid in acetic acid
  8. customThe vial was sealed
  9. stirringstirred for 3 h
  10. customThe volatiles were then evacuated in vacuo
  11. customthe residue was purified via preparatory HPLC

Sources & evidence

ORD record
ord-f2c9d229fcc5477e9c84211779f53f47
Source dataset
uspto-grants-2013_05
Patent number
US08445518B2

Reaction notes

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