Trifluoroacetic acid → N-[4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-2,6-difluoro-4-methoxy-benzamide trifluoroacetate

HRID 521608Notes

Reaction equation

HRID 521608 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([F:13])[C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[NH2:45][C:46]1[CH:62]=[CH:61][C:49]([O:50][CH2:51][CH2:52][NH:53]C(=O)OC(C)(C)C)=[C:48]([C:63]2[N:67]([CH3:68])[N:66]=[CH:65][CH:64]=2)[CH:47]=1.[C:69]([OH:75])([C:71]([F:74])([F:73])[F:72])=[O:70]>C(Cl)Cl>[F:72][C:71]([F:74])([F:73])[C:69]([OH:75])=[O:70].[NH2:53][CH2:52][CH2:51][O:50][C:49]1[CH:61]=[CH:62][C:46]([NH:45][C:4](=[O:6])[C:3]2[C:7]([F:13])=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:2]=2[F:1])=[CH:47][C:48]=1[C:63]1[N:67]([CH3:68])[N:66]=[CH:65][CH:64]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 27782282,6-Difluoro-4-methoxybenzoic 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 67265526N-[4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-2,6-difluoro-4-methoxy-benzamide trifluoroacetateYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

2,6-difluoro-4-methoxybenzoic acid (22.6 mg, 120 μmol) was weighed into a microwave vial and CH2Cl2 (1 mL) was added followed by HATU (34.3 mg, 90.3 μmol) and Et3N (20 μl, 144 μmol). After stirring 10 minutes, tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamate (20 mg, 60 μmol) was added to the solution. The reaction mixture was heated at 60° C. for one hour. Then, TFA (1 mL) was added and heated for one hour at 90° C. in order to remove the Boc-protecting group from the amine. The solvent was evaporated. The resulting oil was dissolved in DMSO (1 mL) and purified by Prep LC/MS to give N-[4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-2,6-difluoro-4-methoxy-benzamide trifluoroacetate (8.2 mg, 0.02 mmol, 34%) as a white solid. LCMS m/z (%)=403 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.16 (s, 2H), 3.70 (s, 3H), 3.84 (s, 3H), 4.17 (t, J=5.56 Hz, 2H), 6.36 (d, J=1.77 Hz, 1H), 6.89 (d, J=9.85 Hz, 1H), 7.24 (d, J=9.09 Hz, 1H), 7.49 (d, J=1.77 Hz, 1H), 7.63 (d, J=2.78 Hz, 1H), 7.77 (dd, J=9.09, 2.53 Hz, 1H), 7.89 (br. s., 3H), 10.69 (s, 1H), 13.46 (s, 1H).

Workup

  1. additionwas added
  2. temperatureheated for one hour at 90° C. in order
  3. customto remove the Boc-
  4. customThe solvent was evaporated
  5. dissolutionThe resulting oil was dissolved in DMSO (1 mL)
  6. custompurified by Prep LC/MS

Sources & evidence

ORD record
ord-844f036e5cd246a08d5c8889c22bcda1
Source dataset
uspto-grants-2016_05
Patent number
US09328107B2

Reaction notes

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