Hydrogen Bromide → HCID 86267616, compound

HRID 709995Notes

Reaction equation

HRID 709995 reaction equation
[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([O:11]C)[C:8]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][N:23]=[C:22]([C:26]5[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=5)[CH:21]=4)=[C:15]([CH3:32])[N:14]=3)=[CH:7][N:6]=2)[CH2:3][CH2:2]1.Br>C(O)(=O)C>[CH:1]1([NH:4][C:5]2[NH:10][C:9](=[O:11])[C:8]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][N:23]=[C:22]([C:26]5[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=5)[CH:21]=4)=[C:15]([CH3:32])[N:14]=3)=[CH:7][N:6]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 90416603HCID 90416603, compound

Product 1

HCID 86267616HCID 86267616, compoundYield 44.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-cyclopropyl-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (0.082 g, 0.191 mmol) in acetic acid (2 mL) was treated with HBr (0.087 mL, 0.764 mmol) and heated at 90° C. for 4 h. The mixture was cooled to RT, treated with ice, neutralized with satd. NaHCO3 and extracted with EtOAc (3×). The combined organics were washed with brine, dried over MgSO4, concentrated to dryness, treated with MeCN, sonicated, heated to near-boiling and allowed to stand at RT overnight. The resulting solid was collected via filtration. The combined aqueous washes were filtered, the solid washed with water, dried and combined with the above-isolated solid to afford 2-(cyclopropylamino)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (35 mg, 44%). 1H NMR (400 MHz, DMSO-d6): δ 11.09 (br s, 1H), 8.68 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.28 (m, 1H), 8.25 (s, 1H), 7.96 (d, J=0.8 Hz, 1H), 7.66 (br s, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.73-2.68 (m, 1H), 2.34 (s, 3H), 0.75 (m, 2H), 0.55-0.53 (m, 2H); MS (ESI) m/z: 416.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. additiontreated with ice
  3. extractionNaHCO3 and extracted with EtOAc (3×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to dryness
  7. additiontreated with MeCN
  8. customsonicated
  9. temperatureheated
  10. filtrationThe resulting solid was collected via filtration
  11. filtrationThe combined aqueous washes were filtered
  12. washthe solid washed with water
  13. customdried

Sources & evidence

ORD record
ord-3a5c8fec18ea4cdf89160d42fef42b7c
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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