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Potassium Phosphate, Tribasic → 2-(3-(2,4-difluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

HRID 634163
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HRID 634163 반응식
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1B1OC(C)(C)C(C)(C)O1.I[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[S:37][C:38]([S:41]([CH3:44])(=[O:43])=[O:42])=[N:39][N:40]=3)[CH:34]=2)[N:29]([S:45]([C:48]2[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH:28]=1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.CC(O)C.O>[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[S:37][C:38]([S:41]([CH3:44])(=[O:43])=[O:42])=[N:39][N:40]=3)[CH:34]=2)[N:29]([S:45]([C:48]2[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH:28]=1
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참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 162176522-(2,4-Difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 683282122-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

생성물 1

HCID 683286122-(3-(2,4-difluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole수율 37.5%

시약·촉매·용매 2

HCID 11714597
Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)
촉매
HCID 21889133Propan-2-ol--water (1/1)용매

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온도
80 °C

실험 절차

A mixture of potassium phosphate tribasic (1.309 g, 6.17 mmol, Aldrich), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.044 g, 0.062 mmol, Aldrich), 2,4-difluorophenylboronic acid pinacol ester (0.740 g, 3.08 mmol, Aldrich), 2-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (1.15 g, 2.056 mmol), and IPA/H2O (70%, 10 mL) was heated at 80° C. for 2 h. The mixture was partially concentrated to remove most IPA, and the aq. layer was extracted with DCM. The aq. layer was acidified with 2M HCl and extracted again with DCM. The combined DCM fractions were evaporated and purified by prep HPLC (50-95% AcCN/H2O/0.1% TFA) to give 2-(3-(2,4-difluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (0.42 g, 0.770 mmol, 37.4%) as a light yellow solid. MS (ESI, pos. ion) m/z 546 (M+1).

후처리

  1. concentrationThe mixture was partially concentrated
  2. customto remove most IPA
  3. extractionthe aq. layer was extracted with DCM
  4. extractionextracted again with DCM
  5. customThe combined DCM fractions were evaporated
  6. custompurified by prep HPLC (50-95% AcCN/H2O/0.1% TFA)

출처 및 근거

ORD 기록
ord-865d605dfff24052b33096189df91e88
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09321756B2

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