Ethanamine, 2,2,2-trifluoro- → HCID 89657456, compound

HRID 930948Notes

Reaction equation

HRID 930948 reaction equation
[F:1][C:2]1([F:32])[CH2:4][CH:3]1[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH2:16][CH3:17])(=[O:15])=[O:14])=[CH:9][C:8]=1[C:18]1[C:19]2[CH:28]=[C:27]([C:29](O)=[O:30])[NH:26][C:20]=2[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=1.C(Cl)(=O)C(Cl)=O.[F:39][C:40]([F:44])([F:43])[CH2:41][NH2:42]>ClCCl.CN(C)C=O>[F:1][C:2]1([F:32])[CH2:4][CH:3]1[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH2:16][CH3:17])(=[O:14])=[O:15])=[CH:9][C:8]=1[C:18]1[C:19]2[CH:28]=[C:27]([C:29]([NH:42][CH2:41][C:40]([F:44])([F:43])[F:39])=[O:30])[NH:26][C:20]=2[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=1

Participants

6

Reactant 3

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 65578Oxalyl chlorideHCID 89657531HCID 89657531, compound

Product 1

HCID 89657456HCID 89657456, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 327d (0.070 g, 0.15 mmol) in anhydrous dichloromethane (5 mL) were added oxalyl chloride (0.026 mL, 0.300 mmol) and dimethylformamide (0.581 μl, 7.50 μmol). The reaction mixture was stirred at ambient temperature for 2 hours and then evaporated. The residue was dissolved in dichloromethane (5 mL) and treated with 2,2,2-trifluoroethylamine (0.048 mL, 0.600 mmol) and the mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between water (15 mL) and ethyl acetate (25 mL). The aqueous layer was extracted with additional ethyl acetate (15 mL) twice. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase HPLC (C18, mobile phase A:water (10 mM NH4HCO3); B: acetonitrile, Gradient 25-60% B in A) to give the title compound (70 mg, 85%). 1H NMR (400 MHz, CD3OD) δ ppm 7.96-7.90 (m, 2H), 7.66-7.25 (m, 2H), 6.92 (s, 1H), 4.29 (t, J=7.5 Hz, 1H), 4.16 (t, J=9.2 Hz, 1H), 4.05 (tt, J=9.2, 4.5 Hz, 2H), 3.72 (s, 3H), 3.22 (q, J=7.4 Hz, 2H), 2.00 (td, J=12.0, 7.3 Hz, 1H), 1.58-1.46 (m, 1H), 1.32-1.25 (m, 4H). MS (ESI+) m/z 548.1 (M+H)+.

Workup

  1. customevaporated
  2. dissolutionThe residue was dissolved in dichloromethane (5 mL)
  3. stirringthe mixture was stirred at ambient temperature overnight
  4. customThe reaction mixture was partitioned between water (15 mL) and ethyl acetate (25 mL)
  5. extractionThe aqueous layer was extracted with additional ethyl acetate (15 mL) twice
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC (C18, mobile phase A

Sources & evidence

ORD record
ord-7401f7c8c4294f0098bc836a91986fac
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

Loading…