Hydrochloric Acid → 4,5-Dimethyl-furan-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

HRID 521618Notes

Reaction equation

HRID 521618 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:8]([OH:10])=O)[O:5][C:6]=1[CH3:7].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][C:43]1[CH:59]=[CH:58][C:46]([O:47][CH2:48][CH2:49][NH:50]C(=O)OC(C)(C)C)=[C:45]([C:60]2[N:64]([CH3:65])[N:63]=[CH:62][CH:61]=2)[CH:44]=1.Cl.CCOCC>ClCCl>[NH2:50][CH2:49][CH2:48][O:47][C:46]1[CH:58]=[CH:59][C:43]([NH:42][C:8]([C:4]2[O:5][C:6]([CH3:7])=[C:2]([CH3:1])[CH:3]=2)=[O:10])=[CH:44][C:45]=1[C:60]1[N:64]([CH3:65])[N:63]=[CH:62][CH:61]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27749244,5-Dimethylfuran-2-carboxylic 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 578147554,5-Dimethyl-furan-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amideYield 47.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4,5-dimethylfuran-2-carboxylic acid (12.65 mg, 1.2 eq), triethylamine (26.21 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 (376 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 pale yellow solid in 47.3% yield. LCMS m/z (%)=355 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.98 (s, 3H), 2.30 (s, 3H), 3.11-3.20 (m, 2H), 3.71 (s, 3H), 4.16 (t, J=5.31 Hz, 3H), 6.36 (s, 1H), 7.10 (s, 1H), 7.21 (d, J=9.09 Hz, 1H), 7.49 (d, J=2.02 Hz, 1H), 7.49 (d, J=2.02 Hz, 1H), 7.68 (d, J=3.03 Hz, 1H), 7.84 (dd, J=9.09, 2.53 Hz, 1H), 7.86-7.98 (m, 2H), 10.01 (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-bce00563dd9545b98bc4802a8a5d37ee
Source dataset
uspto-grants-2016_05
Patent number
US09328107B2

Reaction notes

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