Hydrogen Bromide → HCID 86268029, compound

HRID 710005Notes

Reaction equation

HRID 710005 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][C@H:31]([N:34]([CH3:36])[CH3:35])[CH2:30]2)[N:4]=1.Br.CC#N>CC(O)=O>[CH3:35][N:34]([CH3:36])[C@H:31]1[CH2:32][CH2:33][N:29]([C:5]2[NH:4][C:3](=[O:2])[C:8]([C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]4[CH:21]=[CH:20][N:19]=[C:18]([C:22]5[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=5)[CH:17]=4)=[C:11]([CH3:28])[N:10]=3)=[CH:7][N:6]=2)[CH2:30]1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 6342AcetonitrileHCID 90417751HCID 90417751, compound

Product 1

HCID 86268029HCID 86268029, compoundYield 62.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

(S)-1-(4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-yl)-N,N-dimethylpyrrolidin-3-amine (0.10 g, 0.21 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 crude was treated with hot MeCN and kept at RT. The solid was filtered, washed with MeCN, and dried under vacuum to obtain (S)-2-(3-(dimethylamino)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 (62 mg, 62.8% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.73 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.29 (m, 1H), 8.26 (s, 1H), 7.97 (s, 1H), 7.53 (d, J=8.6 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.62 (dd, J=5.7, 2.4 Hz, 1H), 3.85 (s, 3H), 3.74 (m, 2H), 3.44 (m, 1H), 3.31 (s, 3H), 3.22 (m, 1H), 2.75 (m, 1H), 2.35 (s, 3H), 2.18 (s, 6H), 2.11 (m, 1H), 1.77 (m, 1H) one proton is missing; MS (ESI) m/z: 473.3 (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. customkept at RT
  10. filtrationThe solid was filtered
  11. washwashed with MeCN
  12. customdried under vacuum

Sources & evidence

ORD record
ord-289f8a23559a472aa8d99aa93456901d
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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