Sodium Bicarbonate → 1-(4-(5,6a-Dimethyl-4-morpholino-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylurea

HRID 2386227Notes

Reaction equation

HRID 2386227 reaction equation
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[N:8]([CH3:18])[C:7](=[O:19])[C:6]3([CH3:24])[CH2:20][O:21][CH2:22][CH2:23][N:5]3[C:4]=2[N:3]=1.[CH3:25][NH:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=1)=[O:28].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]>[CH3:18][N:8]1[C:7](=[O:19])[C:6]2([CH3:24])[CH2:20][O:21][CH2:22][CH2:23][N:5]2[C:4]2[N:3]=[C:2]([C:33]3[CH:32]=[CH:31][C:30]([NH:29][C:27]([NH:26][CH3:25])=[O:28])=[CH:35][CH:34]=3)[N:11]=[C:10]([N:12]3[CH2:13][CH2:14][O:15][CH2:16][CH2:17]3)[C:9]1=2

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 866515682-chloro-5,6a-dimethyl-4-morpholino-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Product 1

HCID 513520721-(4-(5,6a-Dimethyl-4-morpholino-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylureaYield 17.4%

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

2-Chloro-5,6a-dimethyl-4-morpholino-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (23 mg, 0.065 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (21.54 mg, 0.078 mmol), PdCl2(dppf) (9.51 mg, 0.013 mmol) and sodium bicarbonate (1.5 mL, sat.) were mixed in 1,4-dioxane (3 mL). The suspension was heated by microwave irradiation at 100° C. for 30 minutes. After filtration, the solution was purified by mass-triggered preparative HPLC eluted with 20-25% of ACN (containing 0.035% TFA) in water (containing 0.05% TFA) on a Phenomenex Gemini 5 μm C18, 75×30 mm column) to give the title compound (5.3 mg 17% yield) as a pale yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 1.57 (s, 3H) 2.70 (s, 3H) 2.80 (s, 3H) 3.34 (m, 1H) 3.64 (m, 1H) 3.72-3.86 (m, 9H) 4.10 (m, 2H) 4.25 (m, 1H) 7.51 (d, J=8 Hz, 2H) 7.62 (d, J=8 Hz, 2H). MS [M+H] Found 468.

Workup

  1. filtrationAfter filtration
  2. customthe solution was purified by mass-triggered preparative HPLC
  3. washeluted with 20-25% of ACN (containing 0.035% TFA) in water (containing 0.05% TFA) on a Phenomenex Gemini 5 μm C18, 75×30 mm column)

Sources & evidence

ORD record
ord-6d303b1f09b44cea8faab85d6927e1e5
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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