Sodium Carbonate → HCID 51352116, compound

HRID 2386261Notes

Reaction equation

HRID 2386261 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C@H:13]3[CH2:17][O:16]C(C)(C)[O:14]3)[C:7](=[O:20])[C:6]3([CH3:25])[CH2:21][O:22][CH2:23][CH2:24][N:5]3[C:4]=2[N:3]=1.[CH3:26][NH:27][C:28]([NH:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1)=[O:29].C(=O)([O-])[O-].[Na+].[Na+]>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].O1CCOCC1>[OH:14][C@H:13]([CH2:17][OH:16])[CH2:12][N:8]1[C:7](=[O:20])[C:6]2([CH3:25])[CH2:21][O:22][CH2:23][CH2:24][N:5]2[C:4]2[N:3]=[C:2]([C:34]3[CH:33]=[CH:32][C:31]([NH:30][C:28]([NH:27][CH3:26])=[O:29])=[CH:36][CH:35]=3)[N:11]=[CH:10][C:9]1=2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651585HCID 86651585, compound

Product 1

HCID 51352116HCID 51352116, compoundYield 11.6%

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

Combined 2-chloro-5-(((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (0.201 g, 0.545 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.166 g, 0.599 mmol), PdCl2(dppf) (0.080 g, 0.109 mmol), sodium carbonate (saturated in water) (1.5 ml, 0.545 mmol) and dioxane (3 ml). The suspension was heated by microwave irradiation at 100° C. for 45 minutes. The reaction mixture was filtered via syringe filter and purified the title compound 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 concentrated in vacuo to remove about ½ of the total volume and allowed t and let sit at room temperate. After 3 days, the sample was concentrated and purified by HPLC (15-25% of AcCN [containing 0.035% TFA] in water [containing 0.05% TFA], Phenomenex Gemini 5 μm C18, 75×30 mm column) and the product containing fractions were combined, concentrated in vacuo and lyophilized, affording the title compound (27.9 mg, 11.5% yield) as a pale green solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34-1.46 (m, 3H) 2.66 (s, 3H) 3.23-3.36 (m, 1H) 3.36-3.46 (m, 1H) 3.59 (t, J=12.00 Hz, 1H) 3.66-3.74 (m, 1H) 3.74-3.87 (m, 2H) 3.88-4.66 (m, 7H) 6.12 (br. s., 1H) 7.44-7.58 (m, 2H) 8.09-8.23 (m, 2H) 8.28-8.45 (m, 1H) 8.73-8.87 (m, 1 H). MS [M+H] found 443.4.

Workup

  1. filtrationThe reaction mixture was filtered via syringe
  2. filtrationfilter
  3. custompurified the title compound
  4. customwas purified by preparative HPLC (
  5. washeluting with 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)
  6. additionProduct containing fractions
  7. concentrationwere concentrated in vacuo
  8. customto remove about ½ of the total volume
  9. concentrationthe sample was concentrated
  10. custompurified by HPLC (15-25% of AcCN [containing 0.035% TFA] in water [containing 0.05% TFA], Phenomenex Gemini 5 μm C18, 75×30 mm column)
  11. additionthe product containing fractions
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8db9f582f7a54bcf81289bc64e17673b
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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