Hydrogen Bromide → HCID 86270437, compound

HRID 709977Notes

Reaction equation

HRID 709977 reaction equation
[CH2:1]([NH:3][C:4]1[N:9]=[C:8]([O:10]C)[C:7]([C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=4)[CH:20]=3)=[C:14]([CH3:31])[N:13]=2)=[CH:6][N:5]=1)[CH3:2].Br.C([O-])(O)=O.[Na+]>C(O)(=O)C.O>[CH2:1]([NH:3][C:4]1[NH:9][C:8](=[O:10])[C:7]([C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=4)[CH:20]=3)=[C:14]([CH3:31])[N:13]=2)=[CH:6][N:5]=1)[CH3:2]

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 516892Sodium BicarbonateHCID 90416623HCID 90416623, compound

Product 1

HCID 86270437HCID 86270437, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of N-ethyl-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (0.29 g, 0.7 mmol) and 48% aq. HBr (0.32 mL, 2.78 mmol) in acetic acid (5 mL) was heated at 90° C. for 6 h. The mixture was cooled to RT, diluted with water (60 mL), made basic with solid NaHCO3, extracted with 1:1 EtOAc/THF (3×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The residue was stirred with MeCN for 1 h and the resulting solid was collected via filtration to afford 2-(ethylamino)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one as white solid (210 mg, 75%). 1H NMR (400 MHz, DMSO-d6): δ 11.20 (br s, 1H), 8.67 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.24-8.26 (m, 2H), 7.96 (s, 1H), 7.50 (d, J=8.6 Hz, 1H), 7.21 (d, J=2.4 Hz, 1H), 6.88 (br s, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.34-3.32 (m, 2H), 2.34 (s, 3H), 1.12 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 404.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. extractionextracted with 1:1 EtOAc/THF (3×)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. filtrationthe resulting solid was collected via filtration

Sources & evidence

ORD record
ord-857da4c23c064fd98515e6eae5872dd9
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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