Hydrochloric Acid → HCID 51352115, compound

HRID 2386260Notes

Reaction equation

HRID 2386260 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=[O:14])[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+].O[Li].O.Cl>O.CO.O1CCOCC1>[CH3:16][C:12]([N:8]1[C:7](=[O:18])[C:6]2([CH3:23])[CH2:19][O:20][CH2:21][CH2:22][N:5]2[C:4]2[N:3]=[C:2]([C:32]3[CH:31]=[CH:30][C:29]([NH:28][C:26]([NH:25][CH3:24])=[O:27])=[CH:34][CH:33]=3)[N:11]=[CH:10][C:9]1=2)([CH3:17])[C:13]([OH:15])=[O:14]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651583HCID 86651583, compound

Product 1

HCID 51352115HCID 51352115, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To crude 2-(2-chloro-6a-methyl-6-oxo-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-2-methylpropanoic acid (79 mg, about 0.233 mmol, as a mixture with its methylester) was added 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.077 g, 0.28 mmol), Pd(dppf)C12-dichloromethane, 1,4-dioxane (3 mL) and NaHCO3 (sat., 1.5 mL). It was heated under an air-filled balloon (1 atm) at 100° C. (bath temperature) for 1.5 hours and then LiOH.H2O (100 mg) was added and heated continued at 80° C. (bath temperature) for 1 hour and 40 minutes The mixture was diluted with water and MeOH, passed through a microfilter. The filtrate was acidified with concentrated HCl (0.1 mL) to pH<7 and then purified on the HPLC (20-20% of AcCN [containing 0.035% TFA] in water [containing 0.05% TFA], Phenomenex Gemini 5 μm C18, 75×30 mm column) to give 2-methyl-2-(6a-methyl-2-(4-(3-methylureido)phenyl)-6-oxo-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)propanoic acid as a clear semisolid (10.2 mg). 1H NMR (400 MHz, METHANOL-d6) δ ppm 1.55 (s, 3H) 1.68 (s, 3H) 1.81 (s, 3H) 2.80 (s, 3H) 3.49 (m, 1H) 3.69 (dd, J=12, 4 Hz, 1H) 3.74 (d, J=12 Hz, 1H) 4.05 (d, J=12 Hz, 1H) 4.15 (dd, J=12, 4 Hz, 1H) 4.48 (d, J=12 Hz, 1H) 7.62 (d, J=8 Hz, 2H) 8.10 (s, 1H) 8.14 (d, J=8 Hz, 2H). MS [M+H] found 455.4.

Workup

  1. temperatureheated
  2. customcontinued at 80° C.
  3. customfor 1 hour
  4. custompurified on the HPLC (20-20% of AcCN [containing 0.035% TFA] in water [containing 0.05% TFA], Phenomenex Gemini 5 μm C18, 75×30 mm column)

Sources & evidence

ORD record
ord-ec7a7d53831f41188c5f68751884499f
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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