Sulfuric acid magnesium salt (1:1) → 2-[4-(tert-Butyl)-2-(1-Boc-piperidin-4-yloxy)benzylamino]-5-chloro-N-(5-chloropyridin-2-yl)benzamide

HRID 644206Notes

Reaction equation

HRID 644206 reaction equation
[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[C:7]([O:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:27][C:28]1[CH:29]=[CH:30][C:31]([NH:34][C:35](=[O:44])[C:36]2[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=2[NH2:43])=[N:32][CH:33]=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.S([O-])([O-])(=O)=O.[Mg+2].[B-][N+](C)(C)C>C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:43][C:37]2[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:36]=2[C:35]([NH:34][C:31]2[CH:30]=[CH:29][C:28]([Cl:27])=[CH:33][N:32]=2)=[O:44])=[C:7]([O:13][CH:14]2[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:18][CH2:19]2)[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 6327651Borane,N-dimethylmethanamine (1:1)HCID 219064182-Amino-5-chloro-N-(5-chloropyridin-2-yl)benzamideHCID 866342044-(tert-Butyl)-2-(1-Boc-piperidin-4-yloxy)benzaldehyde

Product 1

HCID 685338362-[4-(tert-Butyl)-2-(1-Boc-piperidin-4-yloxy)benzylamino]-5-chloro-N-(5-chloropyridin-2-yl)benzamideYield 87.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

A solution of the 4-(tert-butyl)-2-(1-Boc-piperidine-4-yloxy)benzaldehyde (0.15 g, 0.42 mmol), N-(5-chloropyridin-2-yl)-2-amino-5-chlorobenzamide (0.12 g, 0.42 mmol) and catalytic pyridinium p-toluenesulfonate in toluene (8 mL) was treated with excess magnesium sulfate (0.5 g). The reaction mixture was then heated at 75° C. overnight. The reaction was cooled down to room temperature, filtered, and concentrated in vacuo to an oily residue which was redissolved in acetic acid (1.4 mL). The resulting solution was treated with borane-trimethylamine complex (0.2 g, 2.74 mmol) and stirred at room temperature for 3 h. The reaction mixture was then partition between 5 N aqueous sodium hydroxide and dichloromethane. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo to a residue which was purified on a silica gel chromatotron plate. Elution with ethyl acetate-hexanes (95:5) then (9:1) provided the title compound (0.23 g, 87%) as a yellow oil which foamed up under vacuum. Recrystallization of the oil from ethyl acetate-hexanes provided analytically pure product (0.17 mg) as a pale-yellow crystalline solid.

Workup

  1. temperatureThe reaction was cooled down to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo to an oily residue which
  4. dissolutionwas redissolved in acetic acid (1.4 mL)
  5. customThe reaction mixture was then partition between 5 N aqueous sodium hydroxide and dichloromethane
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with dichloromethane
  8. dry with materialThe combined organic extracts were dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a residue which
  11. customwas purified on a silica gel chromatotron plate
  12. washElution with ethyl acetate-hexanes (95:5)

Sources & evidence

ORD record
ord-4b8f9d4f6aa04e958323a3793c2adbe0
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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