Hydrogen Bromide → HCID 86267408, compound

HRID 709986Notes

Reaction equation

HRID 709986 reaction equation
C[O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5]([NH:29][CH2:30][CH2:31][O:32][CH3:33])[N:4]=1.Br>C(O)(=O)C>[CH3:33][O:32][CH2:31][CH2:30][NH:29][C:5]1[NH:4][C:3](=[O:2])[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 90417572HCID 90417572, compound

Product 1

HCID 86267408HCID 86267408, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-methoxy-N-(2-methoxyethyl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (0.10 g, 0.22 mmol) in acetic acid (5 mL) was treated with HBr (0.10 mL, 0.90 mmol), heated at 90° C. for 4 h, cooled to RT and quenched with ice water. The solution was treated with NaHCO3 and NaCl, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN (3 mL) and the resulting solid was collected via filtration to afford 2-((2-methoxyethyl)amino)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (65 mg, 61%). 1H NMR (400 MHz, DMSO-d6): δ 11.02 (br s, 1H), 8.67 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.29-8.23 (m, 2H), 7.96 (d, J=0.7 Hz, 1H), 7.50 (d, J=8.6 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 6.85 (br s, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.53-3.44 (m, 4H), 3.28 (s, 3H), 2.34 (s, 3H); MS (ESI) m/z: 434.2 (M+H+).

Workup

  1. temperaturecooled to RT
  2. customquenched with ice water
  3. additionThe solution was treated with NaHCO3 and NaCl
  4. extractionextracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. additionThe material was treated with MeCN (3 mL)
  8. filtrationthe resulting solid was collected via filtration

Sources & evidence

ORD record
ord-74b2b5449b3343f380f4578fbfd25dd6
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

Loading…