Acetic Acid → 1-{Dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea

HRID 2207413Notes

Reaction equation

HRID 2207413 reaction equation
[O-:1][C:2]#[N:3].[K+].[NH2:5][C:6]([CH:34]1[CH2:36][CH2:35]1)([CH:31]1[CH2:33][CH2:32]1)[C:7]1[N:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]([NH:20][C:21]3[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=3)[CH:16]=[C:17]([CH3:19])[CH:18]=2)=[CH:9][CH:8]=1.C1COCC1.C(O)(=O)C>C([O-])(O)=O.[Na+].O>[CH:31]1([C:6]([CH:34]2[CH2:36][CH2:35]2)([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[CH:14]=[C:15]([NH:20][C:21]4[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)=[CH:11][N:12]=2)[NH:5][C:2]([NH2:3])=[O:1])[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 11378442Potassium cyanateHCID 118092744N-(3-{6-[amino(dicyclopropyl)methyl]pyridin-3-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 1180926411-{Dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Potassium cyanate (71.1 mg, 0.876 mmol) was added to a mixture of N-(3-{6-[amino(dicyclopropyl)methyl]pyridin-3-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (257 mg, 0.584 mmol), THF (4.00 mL), acetic acid (0.050 ml, 0.876 mmol), and water (2.00 mL) and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with saturated aqueous NaHCO3 (20.0 mL) and extracted with ethyl acetate (50.0 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-20% methanol in ethyl acetate) and the isolated material was then triturated with ethyl acetate (4.00 mL) and methanol (0.50 mL) to yield 1-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea. MS APCI calc'd for C25H26F3N6O [M+H]+ 483. found 483. 1H NMR (500 MHz, CD3OD) δ11.08 (s, 1H), 9.65 (d, J=5.3 Hz, 1H), 9.49 (d, 1H), 8.74 (s, 1H), 8.68 (d, J=11.2 Hz, 1H), 8.47-8.19 (m, 2H), 8.08 (d, J=5.2 Hz, 1H), 7.98 (s, 1H), 6.87 (s, 1H), 6.24 (s, 2H), 3.16 (s, 4H), 2.26 (s, 2H), 1.26 (d, J=25.7 Hz, 3H), 1.10 (d, J=6.0 Hz, 4H).

Workup

  1. extractionextracted with ethyl acetate (50.0 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (0-20% methanol in ethyl acetate)
  7. customthe isolated material was then triturated with ethyl acetate (4.00 mL) and methanol (0.50 mL)

Sources & evidence

ORD record
ord-38523118f55c48c5b02bec89fdf89e29
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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