Sodium Bicarbonate → HCID 51353297, compound

HRID 2386264Notes

Reaction equation

HRID 2386264 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:7](=[O:18])[CH:6]3[CH2:19][O:20][CH2:21][CH2:22][N:5]3[C:4]=2[N:3]=1.[CH3:23][NH:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1)=[O:26].[C:43](=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:23][NH:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[N:11]=[CH:10][C:9]3[N:8]([CH:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)[C:7](=[O:18])[C:6]4([CH3:43])[CH2:19][O:20][CH2:21][CH2:22][N:5]4[C:4]=3[N:3]=2)=[CH:30][CH:29]=1)=[O:26]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651587HCID 86651587, compound

Product 1

HCID 51353297HCID 51353297, compoundYield 28.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a microwave reaction vial, 2-chloro-5-(tetrahydro-2H-pyran-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (0.0258 g, 0.079 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.024 g, 0.087 mmol), PdCl2(dppf) (0.012 g, 0.016 mmol) and sodium bicarbonate (saturated solution) (0.3 ml, 0.079 mmol) were suspended in dioxane (0.794 ml). The suspension was heated by microwave irradiation at 100° C. for 1 h. The reaction mixture was cooled and purified by preparative HPLC (eluting with 15-25% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column). The clean fractions were combined, concentrated in vacuo and lyophilized, affording the title compound (10.0 mg, 28.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.56-1.73 (m, 2H) 2.61-2.70 (m, 3H) 3.01 (td, J=12.82, 3.66 Hz, 1 H) 3.35-3.46 (m, 1H) 3.46-3.62 (m, 3H) 3.74-3.89 (m, 1H) 3.89-4.04 (m, 2H) 4.14-4.30 (m, 4H) 4.38 (ddt, J=11.81, 7.89, 4.04, 4.04 Hz, 1H) 4.48 (d, J=12.13 Hz, 1H) 6.13 (br. s., 1H) 7.52 (d, J=8.84 Hz, 2H) 8.13-8.20 (m, 2H) 8.40 (s, 1H) 8.81 (s, 1H). MS [M+H] found 439.4.

Workup

  1. customIn a microwave reaction vial
  2. temperatureThe reaction mixture was cooled
  3. custompurified by preparative HPLC (
  4. washeluting with 15-25% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-72f2d38487b7485487b29d79c8e164ce
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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