HCID 57816684, compound → HCID 44230108, compound

HRID 420088Notes

Reaction equation

HRID 420088 reaction equation
[CH2:1]([N:7]([CH3:56])[C:8]([C@@H:10]1[CH2:14][C@H:13]([O:15][C:16]2[C:25]3[C:20](=[C:21]([CH3:28])[C:22]([O:26][CH3:27])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:29]3[S:30][CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[N:33]=3)[CH:17]=2)[CH2:12][N:11]1[C:38]([NH:40][C@:41]1([C:46](=[O:55])[NH:47][S:48]([C:51]2([CH3:54])[CH2:53][CH2:52]2)(=[O:50])=[O:49])[CH2:43][C@H:42]1[CH:44]=[CH2:45])=[O:39])=[O:9])[CH2:2][CH2:3][CH2:4]C=C>ClC(Cl)C>[CH3:27][O:26][C:22]1[C:21]([CH3:28])=[C:20]2[C:25]([C:16]([O:15][C@@H:13]3[CH2:12][N:11]4[C@H:10]([C:8](=[O:9])[N:7]([CH3:56])[CH2:1][CH2:2][CH2:3][CH2:4][CH:45]=[CH:44][C@H:42]5[C@:41]([C:46]([NH:47][S:48]([C:51]6([CH3:54])[CH2:53][CH2:52]6)(=[O:49])=[O:50])=[O:55])([NH:40][C:38]4=[O:39])[CH2:43]5)[CH2:14]3)=[CH:17][C:18]([C:29]3[S:30][CH:31]=[C:32]([C:34]([F:36])([F:37])[F:35])[N:33]=3)=[N:19]2)=[CH:24][CH:23]=1

Participants

3

Reactant 1

HCID 57816684HCID 57816684, compound

Product 1

HCID 44230108HCID 44230108, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
75 °C

Procedure

Compound 129 (3.91 g) was dissolved in dichloroethane (980 mL) under Ar at room temperature. The solution was degassed with argon and then heated at 73-77° C. Zhan 1B catalyst (1%) in dichloroethane was slowly added to the reaction solution. At 25 min, another 1% of the catalyst in DCE was added. In total, 8% of the catalyst was added over 4 hrs and 20 min. The reaction mixture was treated with 2-mercaptonicotinic acid (“MNA”) (1 g). The reaction mixture was cooled down to room temperature, concentrated under vacuum to ˜100 mL, and then washed with 0.5M aqueous NaHCO3. To the separated organic phase was added MNA (1 g) and the mixture was stirred at room temperature for 55-65 min. The mixture was washed twice with aqueous 0.5M NaHCO3, dried over Na2SO4, and filtered. Charcoal (11 g) was added to the organic solution and the mixture was stirred at room temperature for 15 hrs. The mixture was concentrated under vacuum to ˜10-15 mL and filtered through a silica plug. The crude solid was triturated in warm methanol to give compound 68b (1.1 g) as an off-white solid in 30% yield and 98% purity.

Workup

  1. customThe solution was degassed with argon
  2. additionZhan 1B catalyst (1%) in dichloroethane was slowly added to the reaction solution
  3. additionanother 1% of the catalyst in DCE was added
  4. additionIn total, 8% of the catalyst was added over 4 hrs and 20 min
  5. additionThe reaction mixture was treated with 2-mercaptonicotinic acid (“MNA”) (1 g)
  6. temperatureThe reaction mixture was cooled down to room temperature
  7. concentrationconcentrated under vacuum to ˜100 mL
  8. washwashed with 0.5M aqueous NaHCO3
  9. additionTo the separated organic phase was added MNA (1 g)
  10. washThe mixture was washed twice with aqueous 0.5M NaHCO3
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. additionCharcoal (11 g) was added to the organic solution
  14. stirringthe mixture was stirred at room temperature for 15 hrs
  15. concentrationThe mixture was concentrated under vacuum to ˜10-15 mL
  16. filtrationfiltered through a silica plug
  17. customThe crude solid was triturated in warm methanol

Sources & evidence

ORD record
ord-9bd6c7e8c0ad4eb79b95694ddf2516dd
Source dataset
uspto-grants-2012_01
Patent number
US08093379B2

Reaction notes

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