Diisopropylethylamine → N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,3-difluorophenyl)acetamide

HRID 1428567Notes

Reaction equation

HRID 1428567 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[C:19]([F:22])([F:21])[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31](O)=[O:32])=[C:26]([F:34])[C:25]=1[F:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:31](=[O:32])[CH2:30][C:27]2[CH:28]=[CH:29][C:24]([Br:23])=[C:25]([F:35])[C:26]=2[F:34])=[CH:14][C:13]=1[C:19]([F:20])([F:21])[F:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 299220662-(4-Bromo-2,3-difluorophenyl)acetic acidHCID 904168474-(2-Benzyloxyethoxy)-3-trifluoromethyl-phenylamine

Product 1

HCID 90417511N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,3-difluorophenyl)acetamideYield 29.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

To a solution of 4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)aniline (20 mg, 0.064 mmol), 2-(4-bromo-2,3-difluorophenyl)acetic acid (48.4 mg, 0.077 mmol) and DIEA (0.034 mL, 0.193 mmol) in DCM (3 mL) stirred under a N2 atmosphere at 20° C. was added HATU (29.3 mg, 0.077 mmol) in one charge. The reaction mixture was stirred at 20° C. for 2 h. Then the solution was distributed between DCM and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by preparative TLC (PE/EA=5:1, Rf 0.3) to yield a light yellow solid of N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,3-difluorophenyl)acetamide (12 mg, 0.019 mmol, 29.9% yield): 1H NMR (400 MHz, CDCl3) δ 7.69-7.59 (m, 2H), 7.36-7.24 (m, 6H), 7.05 (t, J=7.3 Hz, 1H), 6.96 (d, J=8.4 Hz, 1H), 4.64 (s, 2H), 4.20 (t, J=4.4 Hz, 2H), 3.86 (t, J=4.8 Hz, 2H), 3.71 (s, 2H); ES-LCMS m/z 546.0 (M+H).

Workup

  1. additioncharge
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative TLC (PE/EA=5:1, Rf 0.3)

Sources & evidence

ORD record
ord-16a2cb2fbb0b43b1b3ad49e6ba642df2
Source dataset
uspto-grants-2015_01
Patent number
US08937071B2

Reaction notes

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