Sodium hydride → 1388893-18-2

HRID 2369417Notes

Reaction equation

HRID 2369417 reaction equation
[CH3:1][N:2]([CH3:10])[CH:3]1[CH2:8][CH2:7][CH:6]([OH:9])[CH2:5][CH2:4]1.[H-].[Na+].Cl[C:14]1[CH:19]=[CH:18][N:17]=[C:16]2[S:20][CH:21]=[CH:22][C:15]=12>CN(C)C=O>[CH3:1][N:2]([CH3:10])[CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:14]2[CH:19]=[CH:18][N:17]=[C:16]3[S:20][CH:21]=[CH:22][C:15]=23)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5980664-Chlorothieno[2,3-b]pyridineHCID 18702099trans-4-(Dimethylamino)cyclohexanol

Product 1

HCID 681103201388893-18-2

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 4-(dimethylamino)cyclohexan-1-ol (127 mg, 0.89 mmol, 1.50 equiv) in N,N-dimethylformamide (15 mL). This was followed by the addition of sodium hydride (71 mg, 1.77 mmol, 3.00 equiv, 60%). The resulting solution was stirred for 30 minutes at 80° C. in an oil bath. 4-chlorothieno[2,3-b]pyridine (100 mg, 0.59 mmol, 1.00 equiv) was added to the mixture. The resulting solution was stirred for 3 h at 120° C. in an oil bath. The reaction was then quenched by the addition of 10 mL of ethanol. The resulting mixture was concentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/methanol (10:1). The resulting product (50 mg) was further purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min, up to 4.7.0% in 13 min, up to 100.0% in 2 min); Detector, uv 254/220 nm. This resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid. MS: (ES, m/z): 277.10 [M+H]+ 1 NMR (300 MHz, CD3OD, ppm): δ 1.49-1.69 (m, 4H), 2.06 (d, J=12.3 Hz, 2H), 2.34 (m, 9H), 4.60 (m, 1H), 7.01 (d, J=5.8 Hz, 1H), 7.38 (d, J=6.0 Hz, 1H), 7.52 (d, J=6.3 Hz, 1H), 8.36 (d, J=5.8 Hz, 1H).

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 3 h at 120° C. in an oil bath
  3. customThe reaction was then quenched by the addition of 10 mL of ethanol
  4. concentrationThe resulting mixture was concentrated under vacuum
  5. customThe residue was purified on a silica gel column with dichloromethane/methanol (10:1)
  6. customThe resulting product (50 mg) was further purified by Prep-HPLC with the following conditions
  7. waitmobile phase, CH3CN and water with 0.05% NH4HCO3 (3.0% water with 0.05% NH4HCO3 up to 3.0% in 1 min
  8. waitup to 4.7.0% in 13 min
  9. waitup to 100.0% in 2 min)
  10. customThis resulted in 9.6 mg (6%) of N,N-dimethyl-4-[thieno[2,3-b]pyridin-4-yloxy]cyclohexan-1-amine as a white solid

Sources & evidence

ORD record
ord-b475afd1e3744188a3485a745252ca30
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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