6,8-Difluoro-2-tetralone → HCID 11676736, compound

HRID 1767025Notes

Reaction equation

HRID 1767025 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[CH2:8][C:7](=O)[CH2:6][CH2:5]2.Cl.[CH3:15][C:16]([C:21]1[S:25][C:24]([NH:26][C:27](=[O:33])[CH:28]([NH2:32])[CH2:29][CH2:30][CH3:31])=[N:23][N:22]=1)([CH3:20])[CH2:17][CH2:18][CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH3-]C#N.[Na+]>ClCCl.CN(C=O)C>[CH3:20][C:16]([C:21]1[S:25][C:24]([NH:26][C:27](=[O:33])[C@@H:28]([NH:32][CH:7]2[CH2:6][CH2:5][C:4]3[C:9](=[C:10]([F:12])[CH:11]=[C:2]([F:1])[CH:3]=3)[CH2:8]2)[CH2:29][CH2:30][CH3:31])=[N:23][N:22]=1)([CH3:15])[CH2:17][CH:18]=[CH2:19]

Participants

7

Reactant 4

HCID 40764316,8-Difluoro-2-tetraloneHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 131726495HCID 131726495, compound

Product 1

HCID 11676736HCID 11676736, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6,8-difluoro-3,4-dihydro-1H-naphthalen-2-one (182 mg, 1 mmol), 2-amino-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide HCl (318 mg, 1.2 mmol), 95% pure sodium triacetoxy borohydride (335 mg, 1.5 mmol) in 7.0 mL of anhydrous dichloromethane and 2 ml of DMF was stirred at rt overnight. The reaction was not complete. The mixture was treated with NaBH3CN (140 mg) and stirred at room temperature for 15 hrs. All starting material and imine intermediate were consumed. The crude solution was diluted with dilute NaOH and extracted with methylene chloride. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography to give the title compound. LC-MS, RT=2.2 min, M+1=449.0. The corresponding HCl salt was prepared as a beige solid.

Workup

  1. stirringstirred at room temperature for 15 hrs
  2. customAll starting material and imine intermediate were consumed
  3. additionThe crude solution was diluted with dilute NaOH
  4. extractionextracted with methylene chloride
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude products were purified by silica gel column chromatography

Sources & evidence

ORD record
ord-def2b7af51514e9a8b6f796d808442e6
Source dataset
uspto-grants-2007_06
Patent number
US07232820B2

Reaction notes

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