Acetic Acid → HCID 57860929, compound

HRID 644231Notes

Reaction equation

HRID 644231 reaction equation
[C:1]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([NH:11][C:12]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:13]=2[C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=2)=[O:15])=[O:10])=[C:7]([O:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C=O.[C:40](O)(=O)C>CO>[C:1]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([NH:11][C:12]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:13]=2[C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=2)=[O:15])=[O:10])=[C:7]([O:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:40])[CH2:34][CH2:33]2)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 176Acetic Acid2×HCID 712Formaldehyde2×HCID 57860822HCID 57860822, compound

Product 1

HCID 57860929HCID 57860929, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The 2-[4-tert-butyl-2-(piperidin-4-yloxy)-benzoylamino]-N-(5-chloropyridin-2-yl)-5-fluorobenzamide (450 mg, 0.86 mmol) was placed in a dry flask and diluted with dry MeOH (0.95 mL). Paraformaldehyde (54.0 mg, 1.8 mmol) and NaCNBH4 (167.0 mg, 2.7 mmol) were added, followed by acetic acid (0.5 mL). The reaction was allowed to stir for 18 h. More paraformaldehyde (54.0 mg), NaCNBH4 (107.0 mg) and acetic acid (1.0 mL) were added, and the reaction was stirred another 18 hrs under N2 at room temperature. The solvents were removed in vacuo, and the residue was diluted with H2O (5.0 mL). The flask was cooled in an ice bath while the pH was adjusted to 8 using saturated sodium bicarbonate. This solution was extracted with EtOAc (5×90 mL). The organics were combined and washed with a saturated solution of sodium bicarbonate and then brine. The organic layer was dried over MgSO4 and the solvents were removed in vacuo to obtain the desired product as a white solid (338.2 mg, 0.63 mmol, 73%).

Workup

  1. stirringthe reaction was stirred another 18 hrs under N2 at room temperature
  2. customThe solvents were removed in vacuo
  3. additionthe residue was diluted with H2O (5.0 mL)
  4. temperatureThe flask was cooled in an ice bath while the pH
  5. extractionThis solution was extracted with EtOAc (5×90 mL)
  6. washwashed with a saturated solution of sodium bicarbonate
  7. dry with materialThe organic layer was dried over MgSO4
  8. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-77deebacab904fc4a3ec5d136014f996
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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