HCID 59817858, compound → HCID 58234038, compound

HRID 881396Notes

Reaction equation

HRID 881396 reaction equation
C[C:2]1[C:6]2[N:7]=[C:8](SC)[N:9]=[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:5]=2[S:4][C:3]=1[CH2:19][N:20]1[CH2:25][CH2:24][N:23]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:22][CH2:21]1.C([Sn](CCCC)(CCCC)[C:35]1[CH:40]=[C:39]([NH:41]C(=O)C)[N:38]=[C:37]([NH:45]C(=O)C)[CH:36]=1)CCC>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[O:14]1[CH2:13][CH2:12][N:11]([C:10]2[C:5]3[S:4][C:3]([CH2:19][N:20]4[CH2:25][CH2:24][N:23]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:22][CH2:21]4)=[CH:2][C:6]=3[N:7]=[C:8]([C:35]3[CH:40]=[C:39]([NH2:41])[N:38]=[C:37]([NH2:45])[CH:36]=3)[N:9]=2)[CH2:16][CH2:15]1

Participants

5

Reactant 2

HCID 59817858HCID 59817858, compoundHCID 66934081HCID 66934081, compound

Product 1

HCID 58234038HCID 58234038, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

7-Methyl-2-(methylthio)-4-morpholino-6-((4-N-methylsulfonylpiperazin-1-yl)methyl)thieno[3,2-d]pyrimidine (0.29 mM) was added to 4-tributylstannyl-2,6-diacetylaminopyridine dissolved in 10 mL 1,2-DME followed by the addition of Cu(I)Br-dimethylsulfide and stirred at room temperature for ten minutes. Finally, Pd(PPH3)4 was added and the reaction mixture was heated to reflux under N2 for 2 hours. Complete product formation was confirmed by LCMS. The reaction was diluted with EtOAc, extracted 1× with water and 1× with 1 M HCl. The combined aqueous layers were basified with 10% w/w KOH and extracted the product with EtOAc, dried over MgSO4, and concentrated in vacuo. This crude product was dissolved in 2 N HCl and heated to reflux for 12 hours to remove the acetyl groups and after concentrating in vacuo and HPLC purification gave 279. MS (Q1) 506 (M+)

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux under N2 for 2 hours
  3. extractionextracted 1× with water and 1× with 1 M HCl
  4. extractionextracted the product with EtOAc
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. dissolutionThis crude product was dissolved in 2 N HCl
  8. temperatureheated
  9. temperatureto reflux for 12 hours
  10. customto remove the acetyl groups
  11. concentrationafter concentrating in vacuo and HPLC purification

Sources & evidence

ORD record
ord-0449f9c7b5724f9eb5cfaaa10f08508b
Source dataset
uspto-grants-2015_03
Patent number
US08993563B2

Reaction notes

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