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Dichloromethane → {4-[2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]-1H-pyrazol-1-yl}acetic acid

HRID 1052264
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HRID 1052264 반응식
Br[C:2]1[N:22]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:5]2=[N:6][CH:7]=[C:8]([CH2:10][CH2:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=3)[N:9]=[C:4]2[CH:3]=1.ClCCl.C([O:39][C:40](=[O:56])[CH2:41][N:42]1[CH:46]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH:44]=[N:43]1)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:4]3[CH:3]=[C:2]([C:45]4[CH:44]=[N:43][N:42]([CH2:41][C:40]([OH:56])=[O:39])[CH:46]=4)[N:22]([S:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)(=[O:25])=[O:24])[C:5]3=[N:6][CH:7]=2)[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=1
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참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 59216326tert-Butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetateHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

생성물 1

HCID 89963529{4-[2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]-1H-pyrazol-1-yl}acetic acid
수율 92%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
88 °C

실험 절차

A stirred mixture of 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (from Example 1, Step 4, 40.0 mg, 79.7 μmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (3.25 mg, 3.98 μmol), tert-butyl[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]acetate (24.5 mg, 79.6 μmol), and potassium phosphate (33.8 mg, 0.159 mmol) in water (0.5 mL)/1,4-dioxane (1.0 mL) was heated at 88° C. After 1 hour, the reaction was quenched with saturated aqueous NH4Cl, extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was dissolved in methylene chloride (1 mL) and trifluoroacetic acid (1 mL) was added at ambient temperature. After 2 hours, the volatiles were removed under vacuum to afford the desired product (40 mg, 92%). LCMS calculated for C27H26N5O6S (M+H)+: m/z=548.2. Found: 548.2.

후처리

  1. customthe reaction was quenched with saturated aqueous NH4Cl
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in methylene chloride (1 mL)
  6. additiontrifluoroacetic acid (1 mL) was added at ambient temperature
  7. waitAfter 2 hours
  8. customthe volatiles were removed under vacuum

출처 및 근거

ORD 기록
ord-fa87fb21575f41c99c653f3fcbab96db
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09388185B2

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