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Potassium Phosphate, Tribasic → N,N-Di(Boc)-3-ethynyl-5-[4-(isopropylsulfonyl)phenyl]pyrazin-2-amine

HRID 78659
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HRID 78659 반응식
Br[C:2]1[N:3]=[C:4]([C:23]#[C:24][Si](C)(C)C)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.[CH:29]([S:32]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)(=[O:34])=[O:33])([CH3:31])[CH3:30].[O-]P([O-])([O-])=O.[K+].[K+].[K+].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>CC#N.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O.C(OCC)(=O)C>[C:23]([C:4]1[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=[C:2]([C:38]2[CH:37]=[CH:36][C:35]([S:32]([CH:29]([CH3:31])[CH3:30])(=[O:34])=[O:33])=[CH:40][CH:39]=2)[N:3]=1)#[CH:24]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 656671Sodium PyrosulfiteHCID 441193274-(Isopropylsulphonyl)benzeneboronic acidHCID 58070279Tert-butyl N-tert-butoxycarbonyl-N-[5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl]carbamate

생성물 1

HCID 59471983N,N-Di(Boc)-3-ethynyl-5-[4-(isopropylsulfonyl)phenyl]pyrazin-2-amine

시약·촉매·용매

4
HCID 178418851HCID 178418851, 화합물촉매HCID 962Water용매2회HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

tert-butyl N-[5-bromo-3-(2-trimethylsilylethynyl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (3 g, 6.377 mmol) and (4-isopropylsulfonylphenyl)boronic acid (1.491 g, 6.536 mmol) were dissolved in MeCN (60.00 mL) then treated with water (12.00 mL) and K3PO4 (2.706 g, 12.75 mmol) then degassed/flushed nitrogen (×5 cycles). Treated with Pd[P(tBu)3]2 (162.9 mg, 0.3188 mmol) and reflushed Vac/Nitrogen ×5. The resulting mixture was stirred at room temperature for 1 h. The reaction mixture was poured quickly into a mixture of ethyl acetate (500 mL), water (90 mL) and 1% aqueous sodium metabisulphite at 4° C., shaken well and the layer separated. The organic fraction was dried over MgSO4, filtered and the filtrate was treated with 3-mercaptopropyl ethyl sulphide on silica (0.8 mmol/g)(1 g), pre-absorbed onto silica gel then purified by column chromatography on silica gel eluting with 30-40% EtOAc/petroleu ether. Product fractions were combined and concentrated in vacuo to leave the product as a yellow/ brown viscous oil. Triturated with petroleum ether and some diethyl ether and a small amount of dichloromethane added. Left to stand at room temperature for 30 min and beige crystals formed, isolated by filtration to leave the product as a beige solid (1.95 g, 61%); 1H NMR (400 MHz, DMSO) d 1.20 (m, 6H), 1.39 (s, 18H), 3.50 (m, 1H), 5.01 (s, 1H), 8.03 (m, 2H), 8.46 (m, 2H) and 9.37 (s, 1H) ppm.

후처리

  1. stirringshaken well
  2. customthe layer separated
  3. dry with materialThe organic fraction was dried over MgSO4
  4. filtrationfiltered
  5. additionthe filtrate was treated with 3-mercaptopropyl ethyl sulphide on silica (0.8 mmol/g)(1 g)
  6. custompre-absorbed onto silica gel
  7. customthen purified by column chromatography on silica gel eluting with 30-40% EtOAc/petroleu ether
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-28689bb3683e4eb9a18ca90aa27776b8
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08841308B2

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