Triethylamine → Gsk 1034702

HRID 447783ノート

反応式

HRID 447783 の反応式
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

参加物

7

反応物 4

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

生成物 1

HCID 16038386Gsk 1034702

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-f0fea5d0162b43f29ed0b2a98925957d
出典データセット
uspto-grants-2013_07
特許番号
US08481566B2

反応ノート

読み込み中…