Hydrogen Bromide → HCID 86268246, compound

HRID 710009Notes

Reaction equation

HRID 710009 reaction equation
[C:1]([NH:5][C:6]1[N:11]=[C:10]([O:12]C)[C:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27]4[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=4)[CH:22]=3)=[C:16]([CH3:33])[N:15]=2)=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].Br>C(O)(=O)C>[C:1]([NH:5][C:6]1[NH:11][C:10](=[O:12])[C:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27]4[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=4)[CH:22]=3)=[C:16]([CH3:33])[N:15]=2)=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 90418082N-(tert-butyl)-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine

Product 1

HCID 86268246HCID 86268246, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-(tert-butyl)-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (0.069 g, 0.155 mmol) in acetic acid (1.5 mL) was treated with HBr (48% aq., 0.071 mL, 0.623 mmol) and heated at 90° C. for 4 h. The mixture was removed from heat, treated with ice and EtOAc, neutralized with satd. NaHCO3, extracted with 1:1 EtOAc/THF (3×) and the combined organics were washed with brine, dried over MgSO4 and concentrated to dryness. The resulting material was treated with MeCN, heated to near-reflux and allowed to stand at RT overnight. The solid was removed via filtration and the filtrate was concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM, then MeOH/EtOAc) to afford 2-(tert-butylamino)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (11 mg, 15%). 1H NMR (400 MHz, DMSO-d6): δ 10.59 (s, 1H), 8.67 (s, 1H), 8.37 (d, J=5.6 Hz, 1H), 8.27-8.22 (m, 2H), 7.97 (s, 1H), 7.52 (d, J=8.9 Hz, 1H), 7.23 (d, J=2.6 Hz, 1H), 6.60 (dd, J=6.1, 2.6 Hz, 1H), 6.52 (s, 1H), 3.84 (s, 3H), 2.34 (s, 3H), 1.41 (s, 9H); MS (ESI) m/z: 432.2 (M+H+).

Workup

  1. customThe mixture was removed
  2. temperaturefrom heat
  3. additiontreated with ice and EtOAc
  4. extractionNaHCO3, extracted with 1:1 EtOAc/THF (3×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated to dryness
  8. additionThe resulting material was treated with MeCN
  9. temperatureheated
  10. temperatureto near-reflux
  11. customThe solid was removed via filtration
  12. concentrationthe filtrate was concentrated to dryness
  13. custompurified twice via silica gel chromatography (MeOH/DCM

Sources & evidence

ORD record
ord-1f8f6fbae54f4fd79ee0058d0590a4e8
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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