Trifluoroacetic acid → HCID 58292991, compound

HRID 511384Notes

Reaction equation

HRID 511384 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]([P:32](=[O:39])([O:36][CH2:37][CH3:38])[O:33][CH2:34][CH3:35])[OH:31])=[CH:26][CH:25]=1.[C:40](O)(C(F)(F)F)=O>CO>[CH3:40][O:31][CH:30]([P:32](=[O:39])([O:33][CH2:34][CH3:35])[O:36][CH2:37][CH3:38])[C:27]1[CH:28]=[CH:29][C:24]([NH:23][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11](=[O:12])[NH:13][CH3:14])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=2)=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 23061737Diethyl P-[(4-aminophenyl)hydroxymethyl]phosphonateHCID 866338612-((2-Chloro-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylbenzamide

Product 1

HCID 58292991HCID 58292991, compoundYield 27.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
105 °C

Procedure

Under N2, a solution of 2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide (40.0 mg, 0.12 mmol) and diethyl [(4-aminophenyl)(hydroxy)methyl]-phosphonate (37.6 mg, 0.15 mmol) in a mixture of TFA (28 uL, 0.36 mmol) and MeOH (0.5 mL) was stirred at 105° C. for 45 min in a Biotage microwave reactor. LC-MS showed that the reaction was complete. The solvents were removed under reduced pressure and to the residue was added sat. NaHCO3 (aq) (2 mL) and DCM (5 mL). Layers were separated and the aqueous layer was extracted with DCM (3×5 mL). The combined organic phases were dried over MgSO4, concentrated, and purified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM) to afford the desired product as a white-colored solid (18.5 mg, yield: 27%). 1H NMR (CD3OD, 400 MHz): δ=1.21 (dt, J=0.8, 7.2 Hz, 3H), 1.30 (t, J=7.2 Hz, 3 H), 2.90 (s, 3 H), 3.35 (s, 3 H), 3.93-4.14 (m, 4 H), 4.61 (d, J=15.2 Hz, 1 H), 7.18 (dt, J=1.2, 7.6 Hz, 1 H), 7.34 (dd, J=2.0, 8.4 Hz, 2 H), 7.49 (dd, J=1.6, 8.4 Hz, 1 H), 7.62-7.66 (m, 3 H), 8.34 (s, 1 H), 8.46 (m, 1 H). MS (ES+): m/z 568.11 [MH+]. HPLC: tR=3.31 min (OpenLynx, polar—5 min).

Workup

  1. customThe solvents were removed under reduced pressure and to the residue
  2. additionwas added sat. NaHCO3 (aq) (2 mL) and DCM (5 mL)
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with DCM (3×5 mL)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM)

Sources & evidence

ORD record
ord-3a132d255faf4e11b6f38dd1963d46f1
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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