Sodium hydride → HCID 118184963, compound

HRID 2178987Notes

Reaction equation

HRID 2178987 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH3:12])[C@H:5]1[CH2:10][CH2:9][C@H:8]([OH:11])[CH2:7][CH2:6]1.Cl[C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:25]=1[C:24]1[CH2:23][CH2:22][CH2:21][C:20]=1[S:19]2>CN(C=O)C>[CH3:3][N:4]([CH3:12])[CH:5]1[CH2:10][CH2:9][CH:8]([O:11][C:14]2[CH:15]=[CH:16][CH:17]=[C:18]3[C:25]=2[C:24]2[CH2:23][CH2:22][CH2:21][C:20]=2[S:19]3)[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118184966HCID 118184966, compoundHCID 178484116HCID 178484116, compound

Product 1

HCID 118184963HCID 118184963, compoundYield 31.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

Sodium hydride (69 mg, 1.73 mmol, 3.00 equiv, 60% dispersion in mineral oil) was treated with trans-4-(dimethylamino)cyclohexan-1-ol (164 mg, 1.15 mmol, 2.00 equiv) in distilled DMF (15 mL) at room temperature for 1 h under nitrogen. Then a solution of 12-chloro-7-thiatricyclo[6.4.0.0^[2,6]]dodeca-1(12),2(6),8,10-tetraene (120 mg, 0.57 mmol, 1.00 equiv) in 3 mL of DMF was added via syringe and the resulting solution was stirred for 2 h at 80° C. in an oil bath. After cooling, the reaction was quenched with water and extracted with 5×50 mL of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (100 mg) was purified by preparative HPLC under the following conditions (Waters): Column: Xbridge Prep C18, 5 μm, 19*50 m; water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 40% CH3CN in 10 min); flow rate: 20 mL/min; UV detection at 254 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired N,N-dimethyl-4-[7-thiatricyclo[6.4.0.0^[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yloxy]cyclohexan-1-amine (56.9 mg) as a brown solid. MS (ES): m/z: 317 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 1.49-1.64 (4H, m), 2.04 (2H, d), 2.29 (2H, d), 2.36 (6H, s), 2.43-2.51 (2H, m), 2.99-3.08 (4H, m), 4.37-4.45 (1H, m), 6.67 (1H, d, J=5.6 Hz), 8.27 (1H, d, J=5.6 Hz).

Workup

  1. temperatureAfter cooling
  2. customthe reaction was quenched with water
  3. extractionextracted with 5×50 mL of dichloromethane
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (100 mg) was purified by preparative HPLC under the following conditions (Waters)
  7. waitwater with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 40% CH3CN in 10 min)
  8. customThe product-containing fractions were collected
  9. custompartially evaporated
  10. customto remove water and CH3CN under reduced pressure
  11. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-abd23e8db02b4b38940700fc6a6bb274
Source dataset
uspto-grants-2015_06
Patent number
US09067948B2

Reaction notes

Loading…