Binap, (A+-)- → 2-(2,2,3,3-Tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-ylamino)-6-(3-acetamidophenyl)pyrazine

HRID 16266Notes

Reaction equation

HRID 16266 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[N:15][CH:14]=[C:13](Cl)[N:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[CH:18]1[C:23]([NH2:24])=[CH:22][C:21]2[O:25][C:26]([F:32])([F:31])[C:27]([F:30])([F:29])[O:28][C:20]=2[CH:19]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[F:30][C:27]1([F:29])[O:28][C:20]2[CH:19]=[CH:18][C:23]([NH:24][C:13]3[N:12]=[C:11]([C:7]4[CH:6]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:10]=[CH:9][CH:8]=4)[CH:16]=[N:15][CH:14]=3)=[CH:22][C:21]=2[O:25][C:26]1([F:31])[F:32]

Participants

6

Reactant 4

HCID 634876Binap, (A+-)-HCID 27765742,2,3,3-Tetrafluoro-1,4-benzodioxin-6-amineHCID 116874302-(3-Acetamidophenyl)-6-chloropyrazineHCID 23676156Sodium t-butoxide

Product 1

HCID 115901392-(2,2,3,3-Tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-ylamino)-6-(3-acetamidophenyl)pyrazineYield 10.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Following Method L, 2-(3-acetamidophenyl)-6-chloropyrazine (4a) (60 mg, 0.24 mmol), 2,2,3,3-tetrafluoro-6-amino-1,4-benzodioxene (78.1 mg, 0.35 mmol), Pd(0)2 dba3 (9 mg, 0.01 mmol), BINAP (50 mg, 0.04 mmol), sodium tert-butoxide (33 mg, 0.34 mmol) and toluene (5 mL) were reacted at 85° C. for 16 hours. Evaporation under vacuo followed. The resulting solid was washed with 50 mL dichloromethane and filtered. The insoluble solid was dissolved in 3 mL of hot ethyl acetate. When this mixture was allowed to cool down in the freezer some crystals appeared. Filtration and washing with 2 mL of cold ethyl acetate gave 10.8 mg of the title compound. Yield: 10.4%. 1 H NMR (250 MHz, DMSO-d6) δ 2.08 (s, 3 H), 7.44 (d, 1 H, J=9.1 Hz), 7.47 (d, 1 H, J=7.8 Hz), 7.59 (bd, 1 H, J=7.6 Hz), 7.704-7.759 (m, 2 H), 7.96 (d, 1 H, 2.4 Hz), 8.21 (s, 1 H), 8.45 (bs, 1 H), 8.51 (s, 1 H), 9.95 (s, 1 H), 10.10 (s, 1 H); 13C NMR (62.9 MHZ, DMSO-d6) δ 24.00, 106.13, 115.92, 117.34, 118.01, 120.13, 121.08, 129.31, 130.04, 130.98, 133.62, 136.16, 136.79, 139.03, 139.99, 147.90, 150.84, 168.40; m/z 435.1 [(M+H)+, calcd for C20H14F4N4O3 434.1].

Workup

  1. customwere reacted at 85° C. for 16 hours
  2. customEvaporation under vacuo
  3. washThe resulting solid was washed with 50 mL dichloromethane
  4. filtrationfiltered
  5. dissolutionThe insoluble solid was dissolved in 3 mL of hot ethyl acetate
  6. temperatureto cool down in the freezer some crystals
  7. filtrationFiltration
  8. washwashing with 2 mL of cold ethyl acetate

Sources & evidence

ORD record
ord-7a5e9676d6c743c7aaed88d03299dace
Source dataset
uspto-grants-2010_06
Patent number
US07737152B2

Reaction notes

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