Oxalyl chloride → 2-[(1-tert-butoxycarbonylpiperidin-4-ylcarbonyl)amino]-N-(5-chloropyridin-2-yl)-5-iodobenzamide

HRID 1247139Notes

Reaction equation

HRID 1247139 reaction equation
[C:1]([N:8]1[CH2:16][CH2:15][CH:11]([C:12]([OH:14])=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[O-].[Na+].C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:28]=1[C:29]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][N:33]=1)=[O:30].C(N(CC)C(C)C)(C)C>CO.ClCCl.CN(C)C=O.CN(C1C=CN=CC=1)C>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][CH:11]([C:12]([NH:26][C:27]2[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:28]=2[C:29]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][N:33]=2)=[O:30])=[O:14])[CH2:15][CH2:16]1)=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

10

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 10942334Sodium MethoxideHCID 219063772-amino-N-(5-chloropyridin-2-yl)-5-iodobenzamide

Product 1

HCID 219066352-[(1-tert-butoxycarbonylpiperidin-4-ylcarbonyl)amino]-N-(5-chloropyridin-2-yl)-5-iodobenzamideYield 62%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of 1-Boc-isonipecotic acid (15.26 g, 66.55 mmol) in methanol (135 mL) was added sodium methoxide (3.8 g, 66.8 mmol). After stirring for 1 h, the solvent was removed in vacuo. A portion of the residue (8.92 g, 35.5 mmol) was suspended in dichloromethane (95 mL) and oxalyl chloride (4 mL, 45 mmol) was added, followed by a couple of drops of N,N-dimethylformamide. After stirring for 1 h, the solvent was removed in vacuo. The residue was suspended in dichloromethane (45 mL) and added to a solution of 2-amino-N-(5-chloropyridin-2-yl)-5-iodobenzamide (8.86 g, 23.7 mmol), N,N-diisopropylethylamine (5 mL, 28 mmol), and 4-(N,N-dimethylamino)pyridine (0.33 g, 2.7 mmol) in dichloromethane (50 mL). After stirring 19 h, the reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was slurried in diethyl ether and filtered to give 8.6 g (62%) of a pink solid.

Workup

  1. customthe solvent was removed in vacuo
  2. stirringAfter stirring for 1 h
  3. customthe solvent was removed in vacuo
  4. stirringAfter stirring 19 h
  5. customthe reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationfiltered

Sources & evidence

ORD record
ord-22dc2d3c1b024b038cd559f40769df37
Source dataset
uspto-grants-2006_10
Patent number
US07129245B2

Reaction notes

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