Sodium Hydroxide → HCID 57654590, compound

HRID 1661837Notes

Reaction equation

HRID 1661837 reaction equation
C(O[C:4]([C:6]1[S:7][C:8]([C:11]2[CH:12]=[CH:13][C:14]3[N:15]([C:17]([C:20]([C:23]4[CH:24]=[CH:25][C:26]5[O:30][CH2:29][CH2:28][C:27]=5[CH:31]=4)([F:22])[F:21])=[N:18][N:19]=3)[N:16]=2)=[CH:9][CH:10]=1)=[O:5])C.[OH-].[Na+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:77][N:78]1[CH2:83][CH2:82][NH:81][CH2:80][CH2:79]1>C1COCC1.CO.ClCCl.O>[O:30]1[C:26]2[CH:25]=[CH:24][C:23]([C:20]([F:21])([F:22])[C:17]3[N:15]4[N:16]=[C:11]([C:8]5[S:7][C:6]([C:4]([N:81]6[CH2:82][CH2:83][N:78]([CH3:77])[CH2:79][CH2:80]6)=[O:5])=[CH:10][CH:9]=5)[CH:12]=[CH:13][C:14]4=[N:19][N:18]=3)=[CH:31][C:27]=2[CH2:28][CH2:29]1

Participants

10

Reactant 6

HCID 14798Sodium HydroxideHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58955253HCID 58955253, compound

Product 1

HCID 57654590HCID 57654590, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

The compound prepared in step b was dissolved in a 2:1 THF/methanol (3 mL) mixture and treated with 2N NaOH (0.15 mL). The mixture was stirred for 3 hours at RT, evaporated in vacuo, diluted with water (10 mL), and acidified with 6 N HCl to pH 2. The white solid precipitates were collected, dried under reduced pressure, dissolved in DMF (3 mL) and treated with HATU (0.12 g, 0.31 mmol), HOBt (24 mg, 0.18 mmol) and DIEA (0.1 mL, 1.04 mmol) respectively. The resulting mixture was stirred at RT for 30 minutes and N-methylpiperazine (0.027 mL, 0.24 mmol) was added. Stirring was continued for an additional hour and water (20 mL) was added. dichloromethane (20 mL) was added and layers separated. The CH2Cl2 layer was dried over MgSO4 and evaporated in vacuo. The residue was purified by reverse phase HPLC (Varian Prostar HPLC, Pursuit prep column, CH3CN/H2O containing 0.1% TFA). The final compound was filtered through a HCO3 cartridge and dried under reduced pressure to provide the title compound.

Workup

  1. customevaporated in vacuo
  2. additiondiluted with water (10 mL)
  3. customThe white solid precipitates
  4. customwere collected
  5. customdried under reduced pressure
  6. dissolutiondissolved in DMF (3 mL)
  7. stirringThe resulting mixture was stirred at RT for 30 minutes
  8. stirringStirring
  9. waitwas continued for an additional hour
  10. customlayers separated
  11. dry with materialThe CH2Cl2 layer was dried over MgSO4
  12. customevaporated in vacuo
  13. customThe residue was purified by reverse phase HPLC (Varian Prostar HPLC, Pursuit prep column, CH3CN/H2O containing 0.1% TFA)
  14. filtrationThe final compound was filtered through a HCO3 cartridge
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-886c049096b245d7a2598a52202c4c4e
Source dataset
uspto-grants-2011_10
Patent number
US08030305B2

Reaction notes

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