Potassium Phosphate, Tribasic → Tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-ethynyl-pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate

HRID 78717Notes

Reaction equation

HRID 78717 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]#[CH:24])[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.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH:42]3[CH2:47][CH2:46][CH2:45][N:44]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:43]3)(=[O:41])=[O:40])=[CH:35][CH:34]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC#N.O>[C:11]([O:10][C:9]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:5]1[N:6]=[CH:7][C:2]([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH:42]3[CH2:47][CH2:46][CH2:45][N:44]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:43]3)(=[O:41])=[O:40])=[CH:35][CH:34]=2)=[N:3][C:4]=1[C:23]#[CH:24])=[O:15])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 58070394tert-butyl N-(5-bromo-3-ethynylpyrazin-2-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 86682773Tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate

Product 1

HCID 86682774Tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-ethynyl-pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-butyl N-(5-bromo-3-ethynyl-pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate (2 g, 5.022 mmol) and tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (2.324 g, 5.148 mmol) were dissolved in MeCN (40.00 mL)/water (8.000 mL). K3PO4 (2.131 g, 10.04 mmol) was added and the mixture was degassed/flushed via nitrogen cycles (×5). Pd[P(tBu)3]2. (128.3 mg, 0.2511 mmol) was added and the reaction mixture placed under an atmosphere of nitrogen using vacuum/nitrogen cycles (×5). The reaction mixture was stirred at ambient temperature for 1 hour and then poured onto a stirred mixture of ethylacetate and saturated aqueous sodium metabisulphite at 10° C. The mixture was stirred for 5 minutes, shaken well and separated. The organic layer was washed with brine (×1), dried over MgSO4, filtered and the solution passed through a Florisil eluting with Ethylacetate. The filtrate was concentrated in vacuo and the residue purified by column chromatography (ISCO Companion, 330 g column, eluting with 0 to 40% Petroleum/Petroleum Ether, loaded in DCM) to give tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-ethynyl-pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate as a beige solid (2.45 g, 76% Yield). H NMR (400.0 MHz, DMSO) δ 9.38 (s, 1H), 8.48 (d, 2H), 8.08 (d, 2H), 5.02 (s, 1H), 4.12-3.88 (m, 1H), 3.76 (br d, 1H), 3.43 (br s, 1H), 2.90-2.78 (m, 2H), 2.09 (br s, 1H), 1.75-1.61 (m, 2H) and 1.38-1.18 (m, 28H) ppm;

Workup

  1. customthe mixture was degassed/flushed via nitrogen cycles (×5)
  2. addition(128.3 mg, 0.2511 mmol) was added
  3. additionpoured onto a stirred mixture of ethylacetate and saturated aqueous sodium metabisulphite at 10° C
  4. stirringThe mixture was stirred for 5 minutes
  5. stirringshaken well
  6. customseparated
  7. washThe organic layer was washed with brine (×1)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue purified by column chromatography (ISCO Companion, 330 g column, eluting with 0 to 40% Petroleum/Petroleum Ether, loaded in DCM)

Sources & evidence

ORD record
ord-4853a54c5baf48d58f8eaaf365d5ff42
Source dataset
uspto-grants-2014_09
Patent number
US08841449B2

Reaction notes

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