Triethylamine → Gsk 1034702

HRID 447783Notes

Reaction equation

HRID 447783 reaction equation
Cl.[F:2][C:3]1[C:11]2[NH:10][C:9](=[O:12])[N:8]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:7]=2[CH:6]=[C:5]([CH3:19])[CH:4]=1.C(N(CC)CC)C.[O:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.ClCCCl>[F:2][C:3]1[C:11]2[NH:10][C:9](=[O:12])[N:8]([CH:13]3[CH2:18][CH2:17][N:16]([CH:30]4[CH2:31][CH2:32][O:27][CH2:28][CH2:29]4)[CH2:15][CH2:14]3)[C:7]=2[CH:6]=[C:5]([CH3:19])[CH:4]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 121599Tetrahydro-4H-pyran-4-one2×HCID 5049666Sodium triacetoxyborohydride2×HCID 686240254-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Product 1

HCID 16038386Gsk 1034702

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

4-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D5) (0.072 mmol, 21 mg) was dissolved in dichloromethane (2 ml) and triethylamine (3 eq., 0.216 mmol, 30 microliters), tetrahydro-4H-pyran-4-one (7 eq., 0.5 mmol, 47 microliters) were added and the mixture was stirred at room temperature for 10 minutes; sodium triacetoxyborohydride (7 eq., 0.5 mmol, 106 mg) was added at room temperature and the mixture was stirred at room temperature for one overnight. Reaction mixture was quenched with NaHCO3 (saturated solution) and diluted with dichloromethane; the two phases were separated and the organic solvent was evaporated to afford the crude product. The crude obtained was dissolved in 1,2-dichloroethane (3 ml) and triethylamine (3 eq., 0.216 mmol, 30 microliters), tetrahydro-4H-pyran-4-one (7 eq., 0.5 mmol, 47 microliters) were added again and the mixture was stirred at room temperature for 10 minutes; sodium triacetoxyborohydride (7 eq., 0.5 mmol, 106 mg) was subsequently added at room temperature and the mixture was stirred at room temperature for 3 extra hours. Reaction mixture was quenched with NaHCO3 (saturated solution) and diluted with dichloromethane; the two phases were separated and the organic solvent was evaporated to afford the crude product that was purified by chromatography (methanol-NH3-dichloromethane) to afford 4-fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 10 mg, 42%, M++H=334, which was converted to the HCl salt using 1M HCl in diethyl ether.

Workup

  1. stirringthe mixture was stirred at room temperature for one overnight
  2. customReaction mixture
  3. customwas quenched with NaHCO3 (saturated solution)
  4. additiondiluted with dichloromethane
  5. customthe two phases were separated
  6. customthe organic solvent was evaporated
  7. customto afford the crude product
  8. customThe crude obtained
  9. stirringthe mixture was stirred at room temperature for 10 minutes
  10. stirringthe mixture was stirred at room temperature for 3 extra hours
  11. customReaction mixture
  12. customwas quenched with NaHCO3 (saturated solution)
  13. additiondiluted with dichloromethane
  14. customthe two phases were separated
  15. customthe organic solvent was evaporated
  16. customto afford the crude product that
  17. customwas purified by chromatography (methanol-NH3-dichloromethane)

Sources & evidence

ORD record
ord-f0fea5d0162b43f29ed0b2a98925957d
Source dataset
uspto-grants-2013_07
Patent number
US08481566B2

Reaction notes

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