Tetrahydro-4H-pyran-4-one → 6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one

HRID 2064215ノート

反応式

HRID 2064215 の反応式
Cl.[CH3:2][C:3]1[C:4]([C:19]([F:22])([F:21])[F:20])=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:7]=2[CH:18]=1.[O:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(N(CC)CC)C>[CH3:2][C:3]1[C:4]([C:19]([F:20])([F:22])[F:21])=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:13][CH2:14][N:15]([CH:26]4[CH2:27][CH2:28][O:23][CH2:24][CH2:25]4)[CH2:16][CH2:17]3)[C:7]=2[CH:18]=1

参加物

6

反応物 3

HCID 121599Tetrahydro-4H-pyran-4-one2 回HCID 5049666Sodium triacetoxyborohydride2 回HCID 69171370HCID 69171370、化合物

生成物 1

HCID 160711346-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒2 回HCID 8471Triethylamine溶媒2 回

実験手順

6-Methyl-1-(4-piperidinyl)-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D60) (2.2 mmol), was dissolved in 1,2-dichloroethane (50 ml) and triethylamine (7 ml), tetrahydro-4H-pyran-4-one (7 eq., 15.4 mmol, 1.4 ml), sodium triacetoxyborohydride (7 eq., ˜3.2 g) were added in that order at room temperature and the mixture was stirred at room temperature for 2 hours. Reaction mixture was quenched with 10 ml of 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 again in 1,2-dichloroethane (50 ml) and triethylamine (7 ml), tetrahydro-4H-pyran-4-one (7 eq., 15.4 mmol, 1.4 ml), sodium triacetoxyborohydride (7 eq., ˜3.2 g) were added at room temperature and the mixture was stirred at room temperature for three hours. Reaction mixture was quenched with 10 ml of 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 6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one, 240 mg, 30%, M++H=384, which was subsequently converted into the hydrochloride salt using HCl solution (1M in diethyl ether, 2 eq).

後処理

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

出典と根拠

ORDレコード
ord-ea2cdb18ae2d46b4b5644911bb00abc4
出典データセット
uspto-grants-2012_10
特許番号
US08288412B2

反応ノート

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