Thionyl Chloride → HCID 178501182、化合物

HRID 518732

反応式

HRID 518732 の反応式
[F:1][C:2]1[CH:31]=[CH:30][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:27]=[CH:26][C:25]([CH2:28]O)=[CH:24][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH:36]1[CH2:41][CH2:40][CH:39]([C:42]([OH:45])([CH3:44])[CH3:43])[CH2:38][CH2:37]1>C(Cl)Cl>[F:1][C:2]1[CH:31]=[CH:30][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:27]=[CH:26][C:25]([CH2:28][N:36]4[CH2:41][CH2:40][CH:39]([C:42]([OH:45])([CH3:44])[CH3:43])[CH2:38][CH2:37]4)=[CH:24][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 24386Thionyl ChlorideHCID 52003212-(4-Piperidyl)-2-propanolHCID 178501185HCID 178501185、化合物

生成物 1

HCID 178501182HCID 178501182、化合物収率 81.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a 0° C. cooled solution of cis-methyl 4-((E)-2-(4-fluorobenzoylimino)-6-(hydroxymethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate (1 g, 2.350 mmol) in DCM (25 mL) was added thionyl chloride (0.858 mL, 11.75 mmol) dropwise, and the reaction was stirred at 0° C. for 30 minutes. After 30 minutes, the solvent was removed at reduced pressure, and the residue was suspended in ACN (5 mL) and re-concentrated to remove residual thionyl chloride. The residue was resuspended in ACN (15 mL), cooled to 0° C., and 2-(piperidin-4-yl)propan-2-ol (1.010 g, 7.05 mmol) and TEA (0.655 mL, 4.70 mmol) were added. The reaction was stirred overnight at RT. After 16 hours, the reaction mixture was concentrated and partitioned between EtOAc and water. The organic layer was concentrated and the residual product was purified by column chromatography, eluting with 0-100% (90:9:1 DCM/MeOH/NH4OH)/DCM to provide cis-methyl 4-((E)-2-(4-fluorobenzoylimino)-6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate as a white powder (1.05 g, 81% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03 (s, 6H), 1.09-1.35 (m, 3H), 1.56-1.91 (m, 8H), 2.21-2.29 (m, 2H), 2.53-2.64 (m, 2H), 2.77-2.95 (m, 3H), 3.50 (s, 2H), 3.77 (s, 3H), 3.99 (s, 1H), 4.74 (br. s., 1H), 7.14 (d, J=6.9 Hz, 1H), 7.26 (dd, J=8.8 Hz, 8.8 Hz, 2H), 7.37-7.58 (m, 2H), 8.26 (dd, J=8.7, 5.9 Hz, 2H), 12.77 (s, 1H). MS, m/z (C31H39FN4O4): calcd, 550.3. found, 551.1 [M+H].

後処理

  1. waitAfter 30 minutes
  2. customthe solvent was removed at reduced pressure
  3. concentrationre-concentrated
  4. customto remove residual thionyl chloride
  5. temperaturecooled to 0° C.
  6. stirringThe reaction was stirred overnight at RT
  7. waitAfter 16 hours
  8. concentrationthe reaction mixture was concentrated
  9. custompartitioned between EtOAc and water
  10. concentrationThe organic layer was concentrated
  11. customthe residual product was purified by column chromatography
  12. washeluting with 0-100% (90:9:1 DCM/MeOH/NH4OH)/DCM

出典と根拠

ORDレコード
ord-05e0fa5a6a57497280b9ea8ba808615f
出典データセット
uspto-grants-2015_08
特許番号
US09115127B2

関連ノート

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