Sodium Bicarbonate → HCID 51353297, compound

HRID 2386266Notes

Reaction equation

HRID 2386266 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])[C:6]3([CH3:23])[CH2:19][O:20][CH2:21][CH2:22][N:5]3[C:4]=2[N:3]=1.[CH3:24][NH:25][C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1)=[O:27].C(=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]>[CH3:24][NH:25][C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([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([CH3:23])[CH2:19][O:20][CH2:21][CH2:22][N:5]4[C:4]=3[N:3]=2)=[CH:31][CH:30]=1)=[O:27]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651588HCID 86651588, compound

Product 1

HCID 51353297HCID 51353297, compoundYield 67.4%

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-6a-methyl-5-(tetrahydro-2H-pyran-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (0.046 g, 0.136 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.041 g, 0.149 mmol), PdCl2(dppf) (0.020 g, 0.027 mmol) and sodium bicarbonate (saturated solution) (0.3 ml, 0.136 mmol) were suspended in dioxane (1.36 ml). The suspension was heated by microwave irradiation at 100° C. for 1 hour, then heated by microwave irradiation at 120° C. for an additional 30 minutes. The reaction was purified by preparative HPLC (eluting with 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column). Product containing fractions were combined, concentrated in vacuo and lyophilized, affording the title compound (41.4 mg, 67.4% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32 (s, 3H) 1.55-1.74 (m, 2H) 2.62-2.70 (m, 3H) 3.25 (td, J=13.14, 4.04 Hz, 1 H) 3.34-3.45 (m, 1H) 3.47-3.72 (m, 3H) 3.87-4.00 (m, 3H) 4.06 (dd, J=11.62, 3.79 Hz, 2 H) 4.19 (dd, J=13.77, 2.15 Hz, 3H) 6.01-6.24 (m, 1H) 7.48-7.57 (m, 2H) 8.13-8.22 (m, 2 H) 8.48 (s, 1H) 8.81 (s, 1H). MS [M+H] found 453.4.

Workup

  1. customIn a microwave reaction vial
  2. temperatureheated by microwave irradiation at 120° C. for an additional 30 minutes
  3. customThe reaction was purified by preparative HPLC (
  4. washeluting with 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)
  5. additionProduct containing fractions
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b279b39d78a94a998afb048d7eb3fecb
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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