Hydrogen Bromide → HCID 86268028, compound

HRID 710004Notes

Reaction equation

HRID 710004 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][C@@H:30]2[CH2:34][O:35][CH3:36])[N:4]=1.Br.CCOCC>CC(O)=O>[CH3:36][O:35][CH2:34][C@H:30]1[CH2:31][CH2:32][CH2:33][N:29]1[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

5

Reactant 3

HCID 260Hydrogen BromideHCID 3283Diethyl EtherHCID 90416640HCID 90416640, compound

Product 1

HCID 86268028HCID 86268028, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

(R)-4-methoxy-2-(2-(methoxymethyl)pyrrolidin-1-yl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidine (96 mg, 0.20 mmol) was dissolved in AcOH (3 mL) and then 48% hydrobromic acid (0.1 mL) was added. The mixture was heated at 90° C. FOR 3.5 hours. The mixture was concentrated and the residue was treated with NaHCO3 solution. The solution was extracted with EtOAc (3×) and the organic was washed with NaHCO3, dried over Na2SO4, filtered and concentrated to obtain the crude. The material was treated with ether and sonicated. The solid was filtered, washed with ether and dried under vacuum to obtain (R)-2-(2-(methoxymethyl)pyrrolidin-1-yl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (58 mg, 60.1% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.15 (br s, 1H), 8.73 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.28 (br s, 1H), 8.26 (s, 1H), 7.97 (s, 1H), 7.53 (m, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.62 (m, 1H), 4.34 (m, 1H), 3.85 (s, 3H), 3.52-3.40 (m, 4H), 3.28 (s, 3H), 2.35 (s, 3H), 1.95 (br d, J=27.5 Hz, 4H); MS (ESI) m/z: 474.3 (M+H+).

Workup

  1. concentrationThe mixture was concentrated
  2. additionthe residue was treated with NaHCO3 solution
  3. extractionThe solution was extracted with EtOAc (3×)
  4. washthe organic was washed with NaHCO3
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain the crude
  9. customsonicated
  10. filtrationThe solid was filtered
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-8064f117b4534cac8ebc6fe203249d71
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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