Sodium Hydroxide → HCID 57654491, compound

HRID 1661836Notes

Reaction equation

HRID 1661836 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][CH:29]=[CH: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[CH:28]=[CH: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 57654561HCID 57654561, compound

Product 1

HCID 57654491HCID 57654491, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

The compound prepared in step e 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 (2 mL) and treated with HATU (0.0.62 g, 0.16 mmol), HOBt (0.013 g, 0.09 mmol) and DIEA (0.06 mL, 0.32 mmol) respectively. The resulting mixture was stirred at RT for 30 minutes and N-Methylpiperazine (0.014 mL, 0.14 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, evaporated in vacuo and chromatographed (CH2Cl2/0-10% MeOH) to yield a solid product. Recrystallization for EtOAc afforded the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J=9.8, 1H), 8.17-8.07 (m, 4H), 7.79 (d, J=9.1 Hz, 1H), 7.65 (dd, J=8.5, 2.1 Hz, 1H), 7.50 (d, J=3.9 Hz, 1H), 7.08 (s, 1H), 3.67 (m, 4H), 3.34 (m, 4H), 2.32 (s, 3H); MS (m/z): 495 (MH+)

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 (2 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. customchromatographed (CH2Cl2/0-10% MeOH)
  14. customto yield a solid product
  15. customRecrystallization for EtOAc

Sources & evidence

ORD record
ord-32ab691883594fc688d7bb90161375e7
Source dataset
uspto-grants-2011_10
Patent number
US08030305B2

Reaction notes

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