HCID 66600223, compound → HCID 66600163, compound

HRID 1621814Notes

Reaction equation

HRID 1621814 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[CH:18]=3)=[CH:15][C:14]([CH:43]([N:45]3[CH2:50][CH2:49][O:48][CH2:47][CH2:46]3)[CH3:44])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]>C(O)(C(F)(F)F)=O.OS(C(F)(F)F)(=O)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[CH:18]=3)=[CH:15][C:14]([CH:43]([N:45]3[CH2:46][CH2:47][O:48][CH2:49][CH2:50]3)[CH3:44])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]

Participants

4

Reactant 1

HCID 66600223HCID 66600223, compound

Product 1

HCID 66600163HCID 66600163, compoundYield 68.3%

Reagents, catalysts & solvents 2

HCID 62406Trifluoromethanesulfonic acidCatalystHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-(1-(4-morpholinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.272 g, 0.400 mmol) in TFA (3 mL) was treated with a few drops of triflic acid and heated at 80° C. for 3 h. After cooling to RT, the reaction mixture was concentrated. A few ice cubes were added and saturated NaHCO3 (aq.) was added until pH of about 7. The aqueous layer was extracted with CH2Cl2/n-BuOH (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was adsorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 30% MeOH in CH2Cl2 to give 120 mg of 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-(1-(4-morpholinyl)ethyl)-3-pyridinyl)-2-methyl-4-pyrimidinamine as a mixture of enantiomers as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.21 (s, 1H); 8.33 (dd, J=13.01, 2.25 Hz, 1H); 8.12-8.21 (m, 2H); 7.96 (d, J=2.15 Hz, 1H); 7.04 (s, 2H); 6.79 (s, 1H); 3.92 (s, 3H); 3.57 (t, J=4.79 Hz, 4H); 3.43 (q, J=6.65 Hz, 1H); 2.51 (s, 3H); 2.38-2.47 (m, 2H); 2.27-2.36 (m, 2H); 1.34 (d, J=6.65 Hz, 3H). m/z (ESI, +ve) 440.1 (M+H)+.

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated
  3. additionA few ice cubes were added
  4. additionsaturated NaHCO3 (aq.) was added until pH of about 7
  5. extractionThe aqueous layer was extracted with CH2Cl2/n-BuOH (3×)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  10. washeluting with a gradient of 0% to 30% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-c93ccd322e8347fc9e8fc6ee6d7ecdb1
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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