Pyridine → 3-[2-(1-tert-Butoxycarbonylpiperidin-4-yloxy)-4-(methylthio)benzoylamino]-N-(5-chloropyridin-2-yl)pyridine-2-carboxamide

HRID 1434828Notes

Reaction equation

HRID 1434828 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:23]=[C:22]([S:24][CH3:25])[CH:21]=[CH:20][C:16]=2[C:17]([OH:19])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[NH2:38][C:39]1[C:40]([C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][N:49]=2)=[O:46])=[N:41][CH:42]=[CH:43][CH:44]=1>ClCCl.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:23]=[C:22]([S:24][CH3:25])[CH:21]=[CH:20][C:16]=2[C:17]([NH:38][C:39]2[C:40]([C:45]([NH:47][C:48]3[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][N:49]=3)=[O:46])=[N:41][CH:42]=[CH:43][CH:44]=2)=[O:19])[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 65578Oxalyl chlorideHCID 115578513-amino-N-(5-chloropyridin-2-yl)pyridine-2-carboxamideHCID 115596842-(1-tert-Butoxycarbonylpiperidin-4-yloxy)-4-(methylthio)benzoic acid

Product 1

HCID 116999433-[2-(1-tert-Butoxycarbonylpiperidin-4-yloxy)-4-(methylthio)benzoylamino]-N-(5-chloropyridin-2-yl)pyridine-2-carboxamideYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

The 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(methylthio)benzoic acid (201 mg, 0.55 mmol) was diluted with dichloromethane (5 mL), pyridine (52 μL, 0.64 mmol), and DMF (2 drops). Oxalyl chloride (52 μL, 0.60 mmol) was added and vigorous bubbling occurred. After about 30 minutes, the reaction was concentrated in vacuo. The residue was diluted with dichloromethane (5 mL) and the 3-amino-N-(5-chloropyridin-2-yl)pyridine-2-carboxamide (123 mg, 0.50 mmol) was added, followed by pyridine (72 μL, 0.64 mmol). The reaction was stirred overnight and then diluted with dichloromethane (50 mL) and washed with water (3×5 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude residue was purified by flash column chromatography (CH2Cl2 through 5% EtOAc/CH2Cl2) to give the desired product as a pale yellow amorphous solid (214 mg, 0.36 mmol, 72%).

Workup

  1. customvigorous bubbling
  2. concentrationthe reaction was concentrated in vacuo
  3. additionThe residue was diluted with dichloromethane (5 mL)
  4. washwashed with water (3×5 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash column chromatography (CH2Cl2 through 5% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-c5f768ae40f34b3499ff8957c58ca06c
Source dataset
uspto-grants-2009_11
Patent number
US07615568B2

Reaction notes

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