HCID 66650463, compound → HCID 59154135, compound

HRID 420094Notes

Reaction equation

HRID 420094 reaction equation
[Cl:1][C:2]1[C:3]([O:53][CH3:54])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[S:13][CH:14]=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[CH:8]=[C:7]2[O:20][C@@H:21]1[CH2:25][N:24]([C:26]([NH:28][C@:29]2([C:34](=[O:42])[NH:35][S:36]([CH:39]3[CH2:41][CH2:40]3)(=[O:38])=[O:37])[CH2:31][C@H:30]2C=C)=[O:27])[C@H:23]([C:43]([N:45]([CH2:47][CH2:48][CH2:49][CH2:50][CH:51]=[CH2:52])[CH3:46])=[O:44])[CH2:22]1.SC1N=CC=CC=1C(O)=O>ClC(Cl)C>[Cl:1][C:2]1[C:3]([O:53][CH3:54])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[S:13][CH:14]=[C:15]([CH:17]([CH3:18])[CH3:19])[N:16]=1)[CH:8]=[C:7]2[O:20][C@@H:21]1[CH2:25][N:24]2[C@H:23]([C:43](=[O:44])[N:45]([CH3:46])[CH2:47][CH2:48][CH2:49][CH2:50][CH:51]=[CH:52][C@H:31]3[C@:29]([C:34]([NH:35][S:36]([CH:39]4[CH2:41][CH2:40]4)(=[O:37])=[O:38])=[O:42])([NH:28][C:26]2=[O:27])[CH2:30]3)[CH2:22]1

Participants

4

Reactant 2

HCID 66650463HCID 66650463, compoundHCID 178524460HCID 178524460, compound

Product 1

HCID 59154135HCID 59154135, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
75 °C

Procedure

Compound 137 (5.5 g) was dissolved in dichloroethane (1.375 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. At 45 min, 2-mercaptonicotinic acid (0.5 eq.) was added. The reaction mixture was cooled down to room temperature, concentrated under vacuum to ˜130 mL, and then washed with 0.5M aqueous NaHCO3. To the separated organic phase was added MNA (0.5 eq.) 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 (5.5 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 crystallized from hot methanol and DCE to give compound 62d (2.87 g) as a white solid in 54% yield and 98% purity. More product was obtained similarly from the filtrate to give 487 mg of a white solid. Thus, the total yield was 63%.

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. waitAt 45 min
  5. temperatureThe reaction mixture was cooled down to room temperature
  6. concentrationconcentrated under vacuum to ˜130 mL
  7. washwashed with 0.5M aqueous NaHCO3
  8. additionTo the separated organic phase was added MNA (0.5 eq.)
  9. washThe mixture was washed twice with aqueous 0.5M NaHCO3
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. additionCharcoal (5.5 g) was added to the organic solution
  13. stirringthe mixture was stirred at room temperature for 15 hrs
  14. concentrationThe mixture was concentrated under vacuum to ˜10-15 mL
  15. filtrationfiltered through a silica plug
  16. customThe crude solid was crystallized from hot methanol and DCE

Sources & evidence

ORD record
ord-396e6226938c404eb3f045c78de0ad56
Source dataset
uspto-grants-2012_01
Patent number
US08093379B2

Reaction notes

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