Hydrogen Peroxide → HCID 59239528, compound

HRID 1697939Notes

Reaction equation

HRID 1697939 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][C@@H:31]3[CH3:36])[C:16]3[CH2:22][CH2:21][N:20]([C:23]([C:25]4([CH3:29])[CH2:28][O:27][CH2:26]4)=O)[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].B.C([O-])(O)=O.[Na+].OO>[OH-].[Na+].C1COCC1>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][C@@H:31]3[CH3:36])[C:16]3[CH2:22][CH2:21][N:20]([CH2:23][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27])[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 6331Borane2×HCID 516892Sodium BicarbonateHCID 59239131HCID 59239131, compound

Product 1

HCID 59239528HCID 59239528, compoundYield 27.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-7-(3-methyloxetane-3-carbonyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (jl) (Example 213) (30 mg, 0.061 mmol), borane (0.5 mL of 1.0 M in THF, 0.5 mmol) and THF (1.5 mL) was heated at reflux for 7 h). Further borane (0.3 mL of 1.0 M in THF, 0.3 mmol) was added, and the solution heated at reflux for 15 h. After cooling to rt, sat. NaHCO3 (1 mL) and 3% aq hydrogen peroxide (1 mL) were added and the mixture stirred vigorously for 3 h. The mixture was diluted with 1 N NaOH (20 ml) and extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with brine (1×10 mL) dried over Na2SO4, filtered and concentrated. The residue was purified by RP-HPLC to afford 8 mg (26%) of the title compound as a colorless solid: 1H NMR (400 MHz, MeOD) δ 8.23-8.09 (m, 2H), 7.53-7.36 (m, 2H), 4.29-4.08 (m, 1H), 3.93 (d, J=11.1Hz, 1H), 3.86-3.61 (m, 6H), 3.58-3.45 (m, 1H), 3.24 (q, J=7.2 Hz, 2H), 2.94-2.77 (m, 1H), 2.77-2.68 (m, 3H), 2.49 (s, 2H), 1.32 (t, J=6.2 Hz, 3H), 1.24-1.06 (m, 3H), 0.95 (s, 6H); LC-MS: m/z=+483 (M+H)+.

Workup

  1. temperatureat reflux for 7 h)
  2. temperaturethe solution heated
  3. temperatureat reflux for 15 h
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. washThe combined organic phases were washed with brine (1×10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-e3a0674b7898434b866c11838baa60e0
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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