Sodium Carbonate → Tert-butyl 4-(5-(3-bis(tert-butoxycarbonyl)amino-6-(2-fluoro-4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)benzyl(methyl)carbamate

HRID 78667Notes

Reaction equation

HRID 78667 reaction equation
[C:1]([O:5][C:6]([N:8]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:9]1[C:10]([C:16]2[O:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]([CH3:36])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:23][CH:22]=3)=[N:18][N:17]=2)=[N:11][C:12](Br)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:44][C:45]1[CH:50]=[C:49]([S:51]([CH:54]([CH3:56])[CH3:55])(=[O:53])=[O:52])[CH:48]=[CH:47][C:46]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:9]1[C:10]([C:16]2[O:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]([CH3:36])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:23][CH:22]=3)=[N:18][N:17]=2)=[N:11][C:12]([C:46]2[CH:47]=[CH:48][C:49]([S:51]([CH:54]([CH3:55])[CH3:56])(=[O:53])=[O:52])=[CH:50][C:45]=2[F:44])=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 59472131HCID 59472131, compoundHCID 674253792-Fluoro-4-(isopropylsulfonyl)phenylboronic acid pinacol ester

Product 1

HCID 59472421Tert-butyl 4-(5-(3-bis(tert-butoxycarbonyl)amino-6-(2-fluoro-4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)benzyl(methyl)carbamateYield 96%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

tert-butyl N-[[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate (100 mg, 0.1512 mmol) was dissolved in DMF (1 mL) and 2-(2-fluoro-4-isopropylsulfonyl-phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (74.44 mg, 0.2268 mmol) and Pd(PPh3)2Cl2 (6.254 mg, 0.01512 mmol) were added. Na2CO3 (226.84 of 2 M, 0.4536 mmol) was added and the reaction heated at 80° C. under an atmosphere of nitrogen for 1 h in a sealed tube. The reaction mixture was partitioned between EtOAc (5 mL) and water (5 mL) and the aqueous layer extracted with EtOAc (2×5 mL). The combined organic extracts were washed with water (3×5 mL), brine (2×5 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 50% EtOAc/Petroleum Ether, loaded in CH2Cl2) to give the product as an off-white solid that was used without further purification (114.4 mg, 96% yield)

Workup

  1. customThe reaction mixture was partitioned between EtOAc (5 mL) and water (5 mL)
  2. extractionthe aqueous layer extracted with EtOAc (2×5 mL)
  3. washThe combined organic extracts were washed with water (3×5 mL), brine (2×5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 50% EtOAc/Petroleum Ether, loaded in CH2Cl2)

Sources & evidence

ORD record
ord-5d3bbc2d961b443b94da9bdd1cb3a558
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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