Pyridine → HCID 57471416, compound

HRID 510543Notes

Reaction equation

HRID 510543 reaction equation
[NH2:1][CH:2]1[CH:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2[CH:9]=[C:8]([CH2:19][NH:20][S:21]([C:24]3[N:25]=[CH:26][N:27]([CH3:29])[CH:28]=3)(=[O:23])=[O:22])[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3]1.N1C=CC=CC=1.Cl[CH2:37][CH2:38][CH2:39][C:40](Cl)=[O:41].[OH-].[Na+]>ClCCl.CN(C1C=CN=CC=1)C>[CH2:12]([CH:11]1[C:10]2[CH:9]=[C:8]([CH2:19][NH:20][S:21]([C:24]3[N:25]=[CH:26][N:27]([CH3:29])[CH:28]=3)(=[O:23])=[O:22])[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3][CH:2]1[N:1]1[CH2:37][CH2:38][CH2:39][C:40]1=[O:41])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 783704-Chlorobutyryl chlorideHCID 57467289HCID 57467289, compound

Product 1

HCID 57471416HCID 57471416, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

N-((7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl)-1-methyl-1H-imidazole-4-sulfonamide (271 mg, 0.66 mmol, cf. 173) was dissolved in dichloromethane (10 mL). Pyridine (0.191 mL, 2.357 mmol) was added. 4-Chlorobutanoyl chloride (0.116 mL, 1.038 mmol) was added dropwise. After 2 h N,N-dimethyl-4-aminopyridine (46 mg, 0.378 mmol) was added and stirring was continued over night. 1 N sodium hydroxide solution was added and the mixture extracted with dichloromethane. The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The crude product was suspended in dry tetrahydrofuran and a suspension of sodium hydride (60% in oil, 179 mg, washed twice with pentane prior to addition) in tetrahydrofuran (3 mL) was added. The reaction mixture was heated to 45° C. for 1 h. Water was added and the mixture was extracted with dichloromethane (3×20 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, dichloromethane, methanol). Yield: 98 mg (0.205 mmol, 46%).

Workup

  1. waitwas continued over night
  2. extractionthe mixture extracted with dichloromethane
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. additiona suspension of sodium hydride (60% in oil, 179 mg
  6. washwashed twice with pentane
  7. additionto addition) in tetrahydrofuran (3 mL)
  8. additionwas added
  9. additionWater was added
  10. extractionthe mixture was extracted with dichloromethane (3×20 mL)
  11. dry with materialThe combined organic extracts were dried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customThe crude product was purified by flash chromatography (silica gel, dichloromethane, methanol)

Sources & evidence

ORD record
ord-fa68cb8c57244aa4947c284bb49aa7d7
Source dataset
uspto-grants-2015_08
Patent number
US09096619B2

Reaction notes

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