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Potassium Phosphate, Tribasic → 1-[2-[3-(3-methanesulfonyl-pyrrolidin-1-yl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

HRID 1677427
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HRID 1677427 반응식
[CH3:1][C:2]([CH3:46])([CH3:45])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([C:14]3[CH:15]=[C:16](OS(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)(=O)=O)[CH:17]=[CH:18][CH:19]=3)[N:12]=2)[N:7]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:6]=1)=[O:4].[CH3:47][S:48]([CH:51]1[CH2:55][CH2:54][NH:53][CH2:52]1)(=[O:50])=[O:49].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:47][S:48]([CH:51]1[CH2:55][CH2:54][N:53]([C:16]2[CH:15]=[C:14]([C:11]3[N:12]=[C:13]4[C:5]([C:3](=[O:4])[C:2]([CH3:1])([CH3:45])[CH3:46])=[CH:6][N:7]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:8]4=[N:9][CH:10]=3)[CH:19]=[CH:18][CH:17]=2)[CH2:52]1)(=[O:50])=[O:49]
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참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 34193563-(Methylsulfonyl)pyrrolidineHCID 595406441,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 3-[7-(2,2-dimethyl-propionyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl ester

생성물 1

HCID 59540957
1-[2-[3-(3-methanesulfonyl-pyrrolidin-1-yl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one
수율 84.5%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
115 °C

실험 절차

A mixture of 1,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 3-[7-(2,2-dimethyl-propionyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl ester (120 mg, 0.17 mmol), 3-methanesulfonyl-pyrrolidine (˜40 mg, 0.26 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (11 mg, 0.02 mmol), and K3PO4 (72 mg, 0.34 mmol) in toluene (1.5 mL) was stirred in a sealed tube under argon at 115° C. overnight. The resulting mixture was partitioned between ethyl acetate and water. The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography using 4 g of silica gel and 20-100% EtOAc in hexanes as eluant to afford 0.08 g of impure 1-[2-[3-(3-methanesulfonyl-pyrrolidin-1-yl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one. M+Na 579.

후처리

  1. customThe resulting mixture was partitioned between ethyl acetate and water
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-439890579911474f86991a3bdc08f501
출처 데이터셋
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08008298B2

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