Hydrazine hydrate (1:1) → HCID 52936138, compound

HRID 513164Notes

Reaction equation

HRID 513164 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:13]=3[NH:12][C:11](=S)[CH:10]([CH2:22][C:23]([NH:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:24])[N:9]=2)=[CH:4][CH:3]=1.O.[NH2:33][NH2:34].C[C:36]([CH3:42])(C)C([O-])([O-])[O-].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:13]=3[N:12]3[C:36]([CH3:42])=[N:33][N:34]=[C:11]3[CH:10]([CH2:22][C:23]([NH:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:24])[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24654Hydrazine hydrate (1:1)2×HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 21927715TrimethylorthoacetateHCID 86671778HCID 86671778, compound

Product 1

HCID 52936138HCID 52936138, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of Intermediate 8 (420 mg, 0.9 mmol) in MeOH (40 mL) at 0° C. was added hydrazine monohydrate (0.22 mL, 4.6 mmol). After 15 min at 0° C., the reaction mixture was allowed to warm RT for 1 h and a further 2.5 equiv. of hydrazine hydrate before being heated to 40° C. for 15 min. The mixture was then concentrated to half volume and water was added. The aqueous layer was extracted with DCM (×2) and the organics were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was then dissolved in MeOH (30 mL) and trimethylorthoacetate (0.17 mL, 1.3 mmol) and PPTS (45 mg, 0.18 mmol) were added. The reaction mixture was refluxed for 45 min before being concentrated under reduced pressure. The crude mixture was dissolved in DCM and washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The crude solid was then purified by flash chromatography on silica gel to give the title compound (70 mg, 16% yield over two steps) as a white solid. Rf=0.5 (DCM/MeOH:90/10). Mp >260° C. LC/HRMS (M+H)+ calculated for C26H2835ClN5O2 478.2010. Found 478.1968. Rt 2.76 min.

Workup

  1. concentrationThe mixture was then concentrated to half volume and water
  2. additionwas added
  3. extractionThe aqueous layer was extracted with DCM (×2)
  4. dry with materialthe organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude product was then dissolved in MeOH (30 mL)
  8. temperatureThe reaction mixture was refluxed for 45 min
  9. concentrationbefore being concentrated under reduced pressure
  10. dissolutionThe crude mixture was dissolved in DCM
  11. washwashed with water
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude solid was then purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-10960c9ddfdf4b7eb71768b7e423b35f
Source dataset
uspto-grants-2015_08
Patent number
US09102677B2

Reaction notes

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