Morpholine → 2-[4-(Morpholin-4-yl)-2-(1-tert-butoxycarbonylpiperidin-4-yloxy)benzoylamino]-N-(5-chloropyridin-2-yl)benzamide

HRID 644170

Reaction equation

HRID 644170 reaction equation
F[C:2]1[CH:26]=[CH:25][C:5]([C:6]([NH:8][C:9]2[CH:24]=[CH:23][CH:22]=[CH:21][C:10]=2[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=2)=[O:12])=[O:7])=[C:4]([O:27][CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)[CH:3]=1.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>C(Cl)Cl>[N:41]1([C:2]2[CH:26]=[CH:25][C:5]([C:6]([NH:8][C:9]3[CH:24]=[CH:23][CH:22]=[CH:21][C:10]=3[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=3)=[O:12])=[O:7])=[C:4]([O:27][CH:28]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]3)[CH:3]=2)[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 685302072-[4-Fluoro-2-(1-tert-butoxycarbonylpiperidin-4-yloxy)benzoylamino]-N-(5-chloropyridin-2-yl)benzamide

Product 1

HCID 685307202-[4-(Morpholin-4-yl)-2-(1-tert-butoxycarbonylpiperidin-4-yloxy)benzoylamino]-N-(5-chloropyridin-2-yl)benzamideYield 57.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
129 °C

Procedure

The 2-[4-fluoro-2-(1-tert-butoxycarbonylpiperidin-4-yloxy)benzoylamino]-N-(5-chloropyridin-2-yl)benzamide (203 mg, 0.35 mmol) was diluted with morpholine (4 mL, 45.9 mmol). The mixture was heated to 129° C. for 2 days. The reaction was diluted with methylene chloride (100 mL) and washed with water (2×10 mL). The aqueous layers were combined and extracted with ethyl acetate (100 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated. The crude residue was purified by flash column chromatography (about 25 g silica, 10% EtOAc/CH2Cl2 to 20% EtOAc/CH2Cl2) to give the desired product (125 mg, 0.20 mmol, 56%) as a white solid.

Workup

  1. washwashed with water (2×10 mL)
  2. extractionextracted with ethyl acetate (100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography (about 25 g silica, 10% EtOAc/CH2Cl2 to 20% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-ea65fd8db0d74ab5bee664b0aed2a242
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Linked notes

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