Hydrogen Bromide → HCID 86267611, compound

HRID 709992Notes

Reaction equation

HRID 709992 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]([N:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[N:4]=1.Br>C(O)(=O)C>[CH3:28][C:11]1[N:10]=[C:9]([C:8]2[C:3](=[O:2])[NH:4][C:5]([N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[N:6][CH:7]=2)[CH:14]=[CH:13][C:12]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)[CH:17]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 90417765HCID 90417765, compound

Product 1

HCID 86267611HCID 86267611, compoundYield 94.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-(pyrrolidin-1-yl)pyrimidine (0.1 g, 0.22 mmol) in acetic acid (3 mL) was treated with HBr (0.1 mL, 0.90 mmol) and heated at 90° C. for 6.5 h. The mixture was cooled to RT, quenched with ice water, neutralized with NaHCO3 to pH=8 and extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness, the resulting material treated with MeCN and the solid was collected via filtration to afford 5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-(pyrrolidin-1-yl)pyrimidin-4(3H)-one (89 mg, 91%). 1H NMR (400 MHz, DMSO-d6): δ 11.21 (s, 1H), 8.73 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.31 (m, 1H), 8.26 (s, 1H), 7.97 (d, J=0.7 Hz, 1H), 7.52 (m, 1H), 7.22 (d, J=2.4 Hz, 1H), 6.61 (d, J=5.6 Hz, 1H), 3.85 (s, 3H), 3.50 (m, 4H), 2.35 (s, 3H), 1.91 (m, 4H); MS (ESI) m/z: 430.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customquenched with ice water
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. additionthe resulting material treated with MeCN
  7. filtrationthe solid was collected via filtration

Sources & evidence

ORD record
ord-e4b1f090ae134fbcb418c3ad8abeff60
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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