Sodium t-butoxide → HCID 58169813, compound

HRID 2386290Notes

Reaction equation

HRID 2386290 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][CH:13]3[CH2:17][CH2:16][O:15][CH2:14]3)[C:7](=[O:18])[C:6]3([CH3:23])[CH2:19][O:20][CH2:21][CH2:22][N:5]3[C:4]=2[N:3]=1.[CH:24]1([NH:27][C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)=[O:29])[CH2:26][CH2:25]1.CC([O-])(C)C.[Na+]>O1CCOCC1.CO>[CH:24]1([NH:27][C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][CH:13]5[CH2:17][CH2:16][O:15][CH2:14]5)[C:7](=[O:18])[C:6]5([CH3:23])[CH2:19][O:20][CH2:21][CH2:22][N:5]5[C:4]=4[N:3]=3)=[CH:33][CH:32]=2)=[O:29])[CH2:26][CH2:25]1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 86651604HCID 86651604, compound

Product 1

HCID 58169813HCID 58169813, compoundYield 15.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-6a-methyl-5-((tetrahydrofuran-3-yl)methyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (390 mg, 1.151 mmol) PdCl2(dppf)-CH2Cl2 (188 mg, 0.230 mmol), 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (417 mg, 1.381 mmol) and sodium 2-methylpropan-2-olate (1.5 ml, 1.151 mmol) were combined in 1,4-dioxane (3 ml). The suspension was heated by microwave irradiation at 100° C. for 30 minutes, the reaction was filtered, cooled, and purified by mass-triggered preparative HPLC using 22-25% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) on a Phenomenex Gemini 5 μm C18, 75×30 mm column). Product containing fractions were evaporated in vacuo to give a residue. The residue was dissolved in methanol for transfer. The solvent was removed under a stream of nitrogen gas to give 85 mg of the title compound as a pale yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 0.48-0.57 (m, 2H) 0.71-0.79 (m, 2H) 1.73 (s, 3H) 1.73 (m, 1H) 2.02-2.14 (m, 1H) 2.61 (m, 1H) 2.68-2.80 (m, 1H) 3.55-3.65 (m, 2H) 3.68 (dd, J=12, 4 Hz, 1H) 3.71-3.81 (m, 3H) 3.84 (d, J=12 Hz, 2H) 3.91-4.05 (m, 2H) 4.08-4.21 (m, 2H) 4.75 (d, J=16 Hz, 1H) 7.67 (d, J=8 Hz, 2H) 8.03 (s, 1H) 8.11 (dd, J=8, 4 Hz, 2 H) [M+H] found 479.

Workup

  1. filtrationthe reaction was filtered
  2. temperaturecooled
  3. custompurified by mass-triggered preparative HPLC
  4. additionProduct containing fractions
  5. customwere evaporated in vacuo
  6. customto give a residue
  7. customThe solvent was removed under a stream of nitrogen gas

Sources & evidence

ORD record
ord-85264197bacd4d24b0b747ce7f00b130
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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