Hydrochloric Acid → 3-(4-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoic acid

HRID 1627261ノート

反応式

HRID 1627261 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([O:24][CH3:25])[CH:18]=3)[C:15]([S:26][CH2:27][C:28]3[C:42]([F:43])=[CH:41][C:31]([C:32]([NH:34][CH2:35][CH2:36][C:37]([O:39]C)=[O:38])=[O:33])=[CH:30][C:29]=3[F:44])=[N:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([O:24][CH3:25])[CH:18]=3)[C:15]([S:26][CH2:27][C:28]3[C:42]([F:43])=[CH:41][C:31]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][C:29]=3[F:44])=[N:14][CH:13]=2)([CH3:10])[CH3:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66741184methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate

生成物 1

HCID 667399793-(4-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoic acid収率 40%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A solution of methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate (0.85 mmol from previous step) in MeOH (10 mL) was treated with a solution of NaOH (0.6 mL of a 5M aqueous solution, 3 mmol) at ambient temperature. After stirring for 100 min, the reaction mixture was added dropwise to 1N HCl. The addition afforded a thick, white oil that separated from the aqueous acid. The aqueous mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude product. This material was purified by flash chromatography (silica gel, MeOH/DCM, 0:100 to 10:90) to afford the title compound (220 mg, 40% yield over three steps) as a white powder. 1H NMR (400 MHz, CDCl3) δ 7.29 (dt, J=9.4, 6.0 Hz, 5H), 7.07 (d, J=2.2 Hz, 1H), 6.95 (dd, J=10.5, 8.6 Hz, 1H), 6.82 (dd, J=8.4, 2.2 Hz, 1H), 6.34-6.25 (m, 1H), 5.94 (dd, J=7.4, 2.4 Hz, 1H), 3.96 (s, 2H), 3.76-3.67 (m, 2H), 3.53 (s, 3H), 2.65 (s, 2H), 1.54 (s, 3H), 1.48 (s, 3H); MS (EI) m/z 652 (MH+).

後処理

  1. additionThe addition
  2. customafforded a thick, white oil
  3. customthat separated from the aqueous acid
  4. extractionThe aqueous mixture was extracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude product
  9. customThis material was purified by flash chromatography (silica gel, MeOH/DCM, 0:100 to 10:90)

出典と根拠

ORDレコード
ord-ae60364e31b949948ebc8369513da710
出典データセット
uspto-grants-2014_07
特許番号
US08785488B2

反応ノート

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