Acetic Acid → ((7R)-7-{(4-fluorobenzyl)[(4-fluorophenyl)acetyl]amino}-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetic acid

HRID 476231

반응식

HRID 476231 반응식
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[NH2:10][C@H:11]1[CH2:30][N:15]2[C:16]3[C:21]([C:22]([CH2:23][C:24]([O:26]CCC)=[O:25])=[C:14]2[CH2:13][CH2:12]1)=[CH:20][CH:19]=[CH:18][CH:17]=3.C([BH3-])#N.[Na+].[C:35]([OH:38])(=O)[CH3:36]>CO>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:10]([C:35](=[O:38])[CH2:36][C:5]2[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)[C@H:11]2[CH2:30][N:15]3[C:16]4[C:21]([C:22]([CH2:23][C:24]([OH:26])=[O:25])=[C:14]3[CH2:13][CH2:12]2)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 58349691(R)-propyl 2-(7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate

생성물 1

HCID 58349706((7R)-7-{(4-fluorobenzyl)[(4-fluorophenyl)acetyl]amino}-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetic acid

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

4-Fluorobenzaldehyde (43.0 μL) was dissolved in MeOH (3.0 mL) and then propyl [(7R)-7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate (231 mg) in MeOH (2.0 mL), sodium cyanoborohydride (50.6 mg) and acetic acid (92.0 μL) were added. The reaction mixture was stirred for overnight at room temperature then quenched with NaOH (1N). The aqueous phase was extracted with EtOAc. The organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/hexanes). The resulting benzylamine (48.0 mg) was dissolved in DCM (2.0 mL) and then DMAP (0.743 mg), (4-fluorophenyl)acetyl chloride (32.8 mg) and triethylamine (17.0 μL) were added to the solution under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h then quenched with ½(sat.) aqueous ammonium chloride. DCM (4.0 mL) was added and the two phases were separated by using a phase separator. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel (ethyl acetate/hexanes) to give the title compound as a yellow oil. The resultant material was dissolved in THF (4.0 mL) and MeOH (2.0 mL) then NaOH (0.283 mL, 1N) were added to the solution. The reaction was stirred for 2.5 h at room temperature and then quenched with HCl (1N). DCM was added and the two phases were separated with a phase separator. The organic layers were evaporated under reduced pressure to provide the title compound._MS (+ESI) m/z: 489.

후처리

  1. customthen quenched with NaOH (1N)
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washThe organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate/hexanes)
  8. dissolutionThe resulting benzylamine (48.0 mg) was dissolved in DCM (2.0 mL)
  9. additionDMAP (0.743 mg), (4-fluorophenyl)acetyl chloride (32.8 mg) and triethylamine (17.0 μL) were added to the solution under nitrogen atmosphere
  10. stirringThe reaction mixture was stirred at room temperature for 2 h
  11. customthen quenched with ½(sat.) aqueous ammonium chloride
  12. additionDCM (4.0 mL) was added
  13. customthe two phases were separated
  14. customThe solvent was evaporated under reduced pressure
  15. customthe residue was purified by column chromatography on silica gel (ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-0cb4ccffa754467997b4ff6c78200ee9
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637671B2

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