Pyridine → 2-[4-(N,N-Dimethylamino)-2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-benzoylamino]-N-(5-chloropyridin-2-yl)benzamide

HRID 644163Notes

Reaction equation

HRID 644163 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]([N:24]([CH3:26])[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].[N:27]1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[Cl:39][C:40]1[CH:45]=[CH:44][C:43]([NH:46][C:47](=[O:55])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=2[NH2:54])=C[CH:41]=1>CN(C=O)C.C(Cl)Cl>[CH3:25][N:24]([C:22]1[CH:21]=[CH:20][C:16]([C:17]([NH:54][C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=2[C:47]([NH:46][C:43]2[CH:44]=[CH:45][C:40]([Cl:39])=[CH:41][N:27]=2)=[O:55])=[O:19])=[C:15]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:23]=1)[CH3:26]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 65578Oxalyl chlorideHCID 6704722-amino-N-(4-chlorophenyl)benzamideHCID 576024362-(1-Tert-butoxycarbonylpiperidin-4-yloxy)-4-(dimethyl-amino)benzoic acid

Product 1

HCID 685339532-[4-(N,N-Dimethylamino)-2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-benzoylamino]-N-(5-chloropyridin-2-yl)benzamideYield 85.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(N,N-dimethyl-amino)benzoic acid (950 mg, 2.61 mmol), pyridine (0.23 mL, 2.86 mmol), DMF (1 drop) and methylene chloride (15 mL) was added oxalyl chloride (0.24 mL, 2.73 mmol) dropwise. After 15 minutes, more pyridine (0.23 mL, 2.86 mmol) was added, followed by the N-(4-chlorophenyl)-2-aminobenzamide (645 mg, 2.61 mmol). The reaction was stirred for 1 hour, diluted with methylene chloride, washed with 50% saturated aqueous sodium bicarbonate, and dried over Na2 SO4. The organic solution was concentrated, chromatographed (2000 g silica, 5% EtOAc/CH2Cl2 to 15% EtOAc/CH2Cl2), and triturated with ether to give the desired product (1.32 g, 83%).

Workup

  1. washwashed with 50% saturated aqueous sodium bicarbonate
  2. customdried over Na2 SO4
  3. concentrationThe organic solution was concentrated
  4. customchromatographed (2000 g silica, 5% EtOAc/CH2Cl2 to 15% EtOAc/CH2Cl2)
  5. customtriturated with ether

Sources & evidence

ORD record
ord-9c2ba8cbeef64b989a018083472f5c02
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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