Hydrochloric Acid → N-[4-(2-Amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-2-oxo-2-p-tolyl-acetamide

HRID 521621Notes

Reaction equation

HRID 521621 reaction equation
[O:1]=[C:2]([C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1)[C:3]([OH:5])=O.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:44][C:45]1[CH:61]=[CH:60][C:48]([O:49][CH2:50][CH2:51][NH:52]C(=O)OC(C)(C)C)=[C:47]([C:62]2[N:66]([CH3:67])[N:65]=[CH:64][CH:63]=2)[CH:46]=1.Cl.CCOCC>ClCCl>[NH2:52][CH2:51][CH2:50][O:49][C:48]1[CH:60]=[CH:61][C:45]([NH:44][C:3](=[O:5])[C:2](=[O:1])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=2)=[CH:46][C:47]=1[C:62]1[N:66]([CH3:67])[N:65]=[CH:64][CH:63]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 1514514-Methylbenzoylformic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67265127tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamate

Product 1

HCID 24889273N-[4-(2-Amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-2-oxo-2-p-tolyl-acetamideYield 32.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The 2-oxo-2-p-tolylacetic acid (14.82 mg, 1.2 eq),), triethylamine (31.45 μL, 3.0 eq) and HATU (34.32 mg, 1.2 eq) were dissolved in 1 mL of dichloromethane and stirred at room temperature for 20 minutes. At this time tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamate (25.0 mg, 75.2 μmol) dissolved in 0.5 mL of dichloromethane was added and the reaction was stirred at room temperature for 18 hr. The solvent was evaporated under a stream of nitrogen and the residue was dissolved in 0.5 mL of ethyl acetate. To this was added 2.0M hydrochloric acid in ether (188 μL, 5 eq) and the reaction was stirred at room temperature overnight. The solvent was evaporated under a stream of nitrogen and the residue was dissolved in 1 mL of dimethylsulfoxide and purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 32.2% yield. LCMS m/z (%)=379 (M+H, 100. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.42 (s, 3H), 3.12-3.21 (m, 2H), 3.71 (s, 3H), 4.19 (t, J=5.56 Hz, 2H), 6.37 (d, J=1.52 Hz, 1H), 7.26 (d, J=9.09 Hz, 1H), 7.42 (d, J=8.59 Hz, 2H), 7.49 (d, J=2.02 Hz, 1H), 7.70 (d, J=2.53 Hz, 1H), 7.82 (dd, J=9.09, 2.53 Hz, 1H), 7.97 (d, J=8.08 Hz, 2H), 10.96 (s, 1H).

Workup

  1. additionwas added
  2. stirringthe reaction was stirred at room temperature for 18 hr
  3. customThe solvent was evaporated under a stream of nitrogen
  4. dissolutionthe residue was dissolved in 0.5 mL of ethyl acetate
  5. stirringthe reaction was stirred at room temperature overnight
  6. customThe solvent was evaporated under a stream of nitrogen
  7. dissolutionthe residue was dissolved in 1 mL of dimethylsulfoxide
  8. custompurified by HPLC
  9. customThe proper fractions were collected

Sources & evidence

ORD record
ord-99da7568873c4324a272726444a71527
Source dataset
uspto-grants-2016_05
Patent number
US09328107B2

Reaction notes

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