Dichloromethane → N-(2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethyl)-1,3,4-thiadiazol-2-amine

HRID 1876919Notes

Reaction equation

HRID 1876919 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:26])([C@@H:14]([CH2:21][CH:22](OC)O)[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1.[S:27]1[CH:31]=[N:30][N:29]=[C:28]1[NH2:32].C(Cl)Cl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(OCC)(=O)C.Cl[Ti](OC(C)C)(OC(C)C)OC(C)C.CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:26])([C@@H:14]([CH2:21][CH2:22][NH:32][C:28]4[S:27][CH:31]=[N:30][N:29]=4)[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 199091,3,4-Thiadiazol-2-amineHCID 5049666Sodium triacetoxyborohydrideHCID 584817592-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol

Product 1

HCID 58481794N-(2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethyl)-1,3,4-thiadiazol-2-amineYield 30%

Reagents, catalysts & solvents 3

HCID 178460663HCID 178460663, compoundCatalystHCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol (18 mg, 0.05 mmol), 1,3,4-thiadiazol-2-amine (10 mg, 0.1 mmol), and anhydrous methylene chloride (0.5 mL) was added chlorotriisopropoxytitanium solution (1 M in hexanes, 0.2 mL, 0.2 mmol) at RT under nitrogen. The mixture was stirred at RT for 15 min before sodium triacetoxyborohydride (106 mg, 0.5 mmol) was added. The mixture was stirred at RT for 1 hr and quenched by the addition of saturated aqueous sodium bicarbonate solution (3 mL). The aqueous layer was separated and extracted with ethyl acetate (3×2 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Prep TLC (silica gel, 50% acetone in ethyl acetate) gave N-(2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethyl)-1,3,4-thiadiazol-2-amine (6 mg, 0.015 mmol, 30% yield) as a solid.

Workup

  1. additionwas added
  2. customquenched by the addition of saturated aqueous sodium bicarbonate solution (3 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (3×2 mL)
  5. dry with materialThe combined organic solutions were dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e8e36df48b36445694f27daae507eaf9
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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