1,4-Dioxane → HCID 51352113, compound

HRID 2386257Notes

Reaction equation

HRID 2386257 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][CH:13]3[CH2:15][CH2:14]3)[C:7](=[O:16])[C@@:6]3([CH3:22])[CH2:17][O:18][CH:19]([CH3:21])[CH2:20][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].O1CCOCC1.C([O-])(O)=O.[Na+]>CO.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].ClCCl>[CH:13]1([CH2:12][N:8]2[C:7](=[O:16])[C@@:6]3([CH3:22])[CH2:17][O:18][C@H:19]([CH3:21])[CH2:20][N:5]3[C:4]3[N:3]=[C:2]([C:31]4[CH:30]=[CH:29][C:28]([NH:27][C:25]([NH:24][CH3:23])=[O:26])=[CH:33][CH:32]=4)[N:11]=[CH:10][C:9]2=3)[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651581HCID 86651581, compound

Product 1

HCID 51352113HCID 51352113, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial containing (R)-2-chloro-5-(cyclopropylmethyl)-6a,9-dimethyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (about 0.4 mmol) was added 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.133 g, 0.48 mmol), Pd(dppf)Cl2-dichloromethane, 1,4-dioxane (1.2 mL) and NaHCO3 (sat., 0.6 mL). It was heated in a microwave at 100° C. for 1 hour 45 minutes and then conventionally at 100° C. (bath temperature) for 3 hours. The mixture was diluted with MeOH, passed through a microfilter. The filtrate was purified on the HPLC (40-60% of AcCN in water containing 10 mM NH4HCO3, Phenomenex Gemini 5 μm C18, 75×30 mm column) to give a mixture containing the title product, which was further purified and resolved on a ChiralPak AD-H (5 μm, 10×250 mm, 25-25% of MeOH in liquid CO2) to give the title compound as a white solid (2.1 mg) and having a retention time of 5.20 minutes on ChiralPak AD-H column (5 μm, 2.1×150 mm, 26% of MeOH in liquid CO2). 1H NMR (400 MHz, METHANOL-d6) δ ppm 0.4-0.56 (m, 4H) 1.22 (m, 1H) 1.34 (d, J=4 Hz, 3H) 1.44 (s, 3H) 2.79 (s, 3H) 2.95 (dd, J=16, 12 Hz, 1H) 3.73 (m, 1H) 3.82 (m, 2H) 3.95 (m, 1H) 4.12 (d, J=12 Hz, 1H) 4.35 (dd, J=12, 4 Hz, 1H) 7.46 (d, J=8 Hz, 2H) 8.19 m (s, 1H) 8.20 (d, J=8 Hz, 2H). MS [M+H] found 437.4.

Workup

  1. customThe filtrate was purified on the HPLC (40-60% of AcCN in water containing 10 mM NH4HCO3, Phenomenex Gemini 5 μm C18, 75×30 mm column)
  2. customto give a mixture

Sources & evidence

ORD record
ord-7e5a7e86c0ca43a8baa8dafd3ea35c7c
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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