3-Iodophenol → (E)-tert-butyl 4-(4-(5-(3-hydroxystyryl)pyrazin-2-ylamino)phenylsulfonyl)piperazine-1-carboxylate

HRID 2199319Notes

Reaction equation

HRID 2199319 reaction equation
[CH:1]([C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([N:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[N:7][CH:8]=1)=[CH2:2].I[C:33]1[CH:34]=[C:35]([OH:39])[CH:36]=[CH:37][CH:38]=1.C1(C)C=CC(P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.CCN(C(C)C)C(C)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:39][C:35]1[CH:34]=[C:33]([CH:38]=[CH:37][CH:36]=1)/[CH:2]=[CH:1]/[C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([N:19]3[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]3)(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[N:7][CH:8]=1

Participants

7

Reactant 4

HCID 122723-IodophenolHCID 13956Phosphine, tris(4-methylphenyl)-HCID 81531DiisopropylethylamineHCID 67324584Tert-butyl 4-(4-(5-vinylpyrazin-2-ylamino)phenylsulfonyl)piperazine-1-carboxylate

Product 1

HCID 67325688(E)-tert-butyl 4-(4-(5-(3-hydroxystyryl)pyrazin-2-ylamino)phenylsulfonyl)piperazine-1-carboxylateYield 78.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 4-(4-(5-vinylpyrazin-2-ylamino)phenylsulfonyl)piperazine-1-carboxylate (40 mg, 0.09 mmol), 3-iodophenol (19 mg, 0.09 mmol), Pd(OAc)2 (1.2 mg, 0.005 mmol), tri-p-tolylphosphine (2.5 mg, 0.008 mmol), and DIEA (31 μL, 0.18 mmol) in DMF (3 ml) was heated at 120° C. for 18 h after which, it was filtered with a pad of celite and partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, celite filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography using (20% to 40% Ethyl acetate/Hexane) as a solvent to afford title compound (38 mg, 78% yield). MS m/z: 538 [M+1].

Workup

  1. filtrationwas filtered with a pad of celite
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over MgSO4, celite
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-c9e2b722eff441f182baf5bc824f27f7
Source dataset
uspto-grants-2016_06
Patent number
US09358231B2

Reaction notes

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