Dichloromethane → Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

HRID 2373713노트

반응식

HRID 2373713 반응식
Br[C:2]1[C:3]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=2)[S:5][CH:6]=1.[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[K+].[K+].ClCCl>O1CCOCC1.O.CCOC(C)=O.CCCCCC>[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:2]1[C:3]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=2)[S:5][CH:6]=1

참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 86607182Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

생성물 1

HCID 86607183Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate수율 74.1%

시약·촉매·용매 4

HCID 962Water용매HCID 8058Hexane용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매2회

실험 절차

Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.200 g, 0.5 mmol) was dissolved in dioxane (3 mL) and 2-chlorophenylboronic acid (0.156 g, 1.0 mmol). K2CO3 (0.207 g, 1.5 mmol) was dissolved in H2O (0.2 mL) and added to the dioxane. The solution was degassed by bubbling argon through the mixture for five minutes. {1,1′-Bis(diphenylphosphino)-ferrocene}dichloropalladium(II) complex with dichloromethane (1:1) (0.012 g, 0.015 mmol) was added and the mixture heated under argon to 70° C. for 3 hours (followed by TLC 15:1 hexane:EtOAc). The solvents were removed and the mixture partitioned between EtOAc and H2O. The EtOAc layer was dried (MgSO4) and absorbed onto silica gel. The product was purified by flash chromatography (20:1 hexane:EtOAc) to yield methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.169 g) as a white solid. mp 57-59° C.; 1H NMR (500 MHz, DMSO-d6) δ: 0.87 (t, 6H, J=7.3 Hz), 1.50 (m, 2H), 1.55 (m, 2H), 3.35 (s, 3H), 3.53 (s, 2H), 3.75 (m, 1H), 7.31 (d, 1H, J=7.2 Hz), 7.43 (m, 3H), 7.59 (m, 3H), 7.96 (d, 2H, J=8.4 Hz), 8.12 (d, 1H, J=8.7 Hz). MS (ES) m/z456.1 ([M+H]+). MS (ES) m/z488.1 ([M+CH3OH+H]+). MS (ES) m/z 911.2 ([2M+H]+). Anal. Calcd for C25H26ClNO3S: C, 65.85; H, 5.75; N, 3.07. Found: C, 65.92; H, 5.96; N, 3.27.

후처리

  1. customThe solution was degassed
  2. customby bubbling argon through the mixture for five minutes
  3. customThe solvents were removed
  4. customthe mixture partitioned between EtOAc and H2O
  5. dry with materialThe EtOAc layer was dried (MgSO4)
  6. customabsorbed onto silica gel
  7. customThe product was purified by flash chromatography (20:1 hexane:EtOAc)

출처 및 근거

ORD 기록
ord-59ed782f7af540ab9671fa07a0656e0f
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07459567B2

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