Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 86658644, compound

HRID 1625719Notes

Reaction equation

HRID 1625719 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]1[CH:27]=[C:28]([CH:36]=[CH:37][C:38]=1[CH:39]=[O:40])[O:29][CH2:30][CH2:31][CH2:32][C:33]([O-:35])=O.[Li+].Cl.[N+:43]([C:46]1[CH:53]=[CH:52][C:49]([CH2:50][NH2:51])=[CH:48][CH:47]=1)([O-:45])=[O:44]>CN(C=O)C.C(N(CC)CC)C>[NH2:25][C:26]1[CH:27]=[C:28]([CH:36]=[CH:37][C:38]=1[CH:39]=[O:40])[O:29][CH2:30][CH2:31][CH2:32][C:33]([NH:51][CH2:50][C:49]1[CH:48]=[CH:47][C:46]([N+:43]([O-:45])=[O:44])=[CH:53][CH:52]=1)=[O:35]

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112524674-Nitrobenzylamine hydrochlorideHCID 58481206HCID 58481206, compound

Product 1

HCID 86658644HCID 86658644, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent

Procedure

HATU (114.1 mg) was added to a 1 mL DMF solution of lithium 4-(3-amino-4-formylphenoxy)-butanoate (68.7 mg), and the reaction was shaken at room temperature for 1 hour. The resulting solution was then added to a 1 mL DMF solution of 4-nitrobenzylamine HCl salt (56.6 mg) and triethylamine (84 μL), with another 1 mL DMF to help transfer. The reaction was stirred at room temperature for 2 hours. Upon completion, the reaction mixture was partitioned between 4 mL of 10% NaCl(aq) and 8 mL of EtOAc. The phases were separated and the aqueous layer was extracted again with 8 mL EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure, affording a crude orange oil. The crude oil was purified by silica gel flash column chromatography with gradient elution of 0-10% MeOH/DCM to give the desired product as a light yellow solid. MS (ESI+): m/z 358.2. 1H NMR (400 MHz, CDCl3): 9.70 (s, 1H), 8.14 (d, J=8.8 Hz, 2H), 7.40 (d, J=8.8 Hz, 2H), 7.35 (d, J=8.4 Hz, 1H), 6.26 (dd, J=2.2 Hz, 8.8 Hz, 1H), 6.20 (br, 2H), 6.03 (d with br, J=2.0 Hz, 2H), 4.54 (d, J=6.0 Hz, 2H), 4.02 (t, J=5.8 Hz, 2H), 2.47 (t, J=7.0 Hz, 2H), 2.17 (quintet, J=6.5 Hz, 2H). 13C NMR (100 MHz, CDCl3): 192.0, 172.2, 164.4, 152.2, 147.2, 145.8, 137.8, 128.2, 123.9, 113.9, 105.3, 98.9, 66.7, 42.8, 32.5, 24.8.

Workup

  1. stirringThe reaction was stirred at room temperature for 2 hours
  2. customUpon completion, the reaction mixture was partitioned between 4 mL of 10% NaCl(aq) and 8 mL of EtOAc
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted again with 8 mL EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customaffording a crude orange oil
  9. customThe crude oil was purified by silica gel flash column chromatography with gradient elution of 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-943f565d063e4ddc98d7e95dd0dbce3d
Source dataset
uspto-grants-2014_07
Patent number
US08785151B2

Reaction notes

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