Hydrogen Bromide → HCID 86267405, compound

HRID 709981Notes

Reaction equation

HRID 709981 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]([O:11]C)[C:8]([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)[CH:21]=3)=[C:15]([CH3:32])[N:14]=2)=[CH:7][N:6]=1)([CH3:3])[CH3:2].Br>C(O)(=O)C>[CH:1]([NH:4][C:5]1[NH:10][C:9](=[O:11])[C:8]([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)[CH:21]=3)=[C:15]([CH3:32])[N:14]=2)=[CH:7][N:6]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 90416592HCID 90416592, compound

Product 1

HCID 86267405HCID 86267405, compoundYield 42.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-isopropyl-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (0.063 g, 0.14 mmol) in acetic acid (5 mL) was treated with HBr (0.066 mL, 0.58 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 1:1 THF/EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN (1 mL), allowed to stand at RT and the resulting solid was collected via filtration to afford 2-(isopropylamino)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (25 mg, 38%). 1H NMR (400 MHz, DMSO-d6): δ 10.8 (br s, 1H), 8.68 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.51 (d, J=8.6 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 6.67 (br s, 1H), 6.61 (d, J=5.6 Hz, 1H), 4.07 (m, 1H), 3.85 (s, 3H), 2.34 (s, 3H), 1.17 (d, J=6.5 Hz, 6H); MS (ESI) m/z: 418.2 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-34fb71747f064385aed39926d2bca98b
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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