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

HRID 2204878Notes

Reaction equation

HRID 2204878 reaction equation
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]

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

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/petroleum 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.

Workup

  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/petroleum ether
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-76bb2981d78f4c24b957d6b15b265c78
Source dataset
uspto-grants-2016_06
Patent number
US09365557B2

Reaction notes

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