Hydrogen Bromide → HCID 86268027, compound

HRID 710003Notes

Reaction equation

HRID 710003 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]([NH:29][C@H:30]([CH3:34])[CH2:31][O:32][CH3:33])[N:4]=1.Br.CC#N>CC(O)=O>[CH3:33][O:32][CH2:31][C@H:30]([NH:29][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)[CH3:34]

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 6342AcetonitrileHCID 90417008HCID 90417008, compound

Product 1

HCID 86268027HCID 86268027, compoundYield 71.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

(R)-4-methoxy-N-(1-methoxypropan-2-yl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (98 mg, 0.21 mmol) was dissolved in AcOH (3 mL) and then hydrobromic acid (0.1 mL, 0.85 mmol) 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×). 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 and washed with MeCN and dried under vacuum to obtain (R)-2-((1-methoxypropan-2-yl)amino)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (67 mg, 59.2% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.85 (s, 1H), 8.67 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.25 (m, 2H), 7.97 (s, 1H), 7.51 (d, J=8.6 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.75 (br s, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 4.19 (m, 1H), 3.85 (s, 3H), 3.38 (m, 2H), 3.30 (s, 3H), 2.34 (s, 3H), 1.15 (d, J=6.7 Hz, 3H); MS (ESI) m/z: 448.2 (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-a9c8b1111ae5410c94f4b0a23b2acdcd
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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