1,4-Dioxane → HCID 51352111, compound

HRID 2386245Notes

Reaction equation

HRID 2386245 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]3[CH2:14][CH2:13]3)[C:7](=[O:15])[C:6]3([CH3:20])[CH2:16][O:17][CH2:18][CH2:19][N:5]3[C:4]=2[N:3]=1.O1CCOCC1.[CH3:27][NH:28][C:29]([NH:31][C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1)=[O:30].C([O-])(O)=O.[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].O>[CH:12]1([N:8]2[C:7](=[O:15])[C:6]3([CH3:20])[CH2:16][O:17][CH2:18][CH2:19][N:5]3[C:4]3[N:3]=[C:2]([C:35]4[CH:34]=[CH:33][C:32]([NH:31][C:29]([NH:28][CH3:27])=[O:30])=[CH:37][CH:36]=4)[N:11]=[CH:10][C:9]2=3)[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651573HCID 86651573, compound

Product 1

HCID 51352111HCID 51352111, compoundYield 19.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

A microwave vial equipped with a magnetic stirrer was added 2-chloro-5-cyclopropyl-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (100 mg, 0.339 mmol), 1,4-dioxane (2 ml), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (141 mg, 0.509 mmol), NaHCO3 (585 μl), followed by PdCl2(dppf) (12.41 mg, 0.017 mmol). The reaction was irradiated in the microwave at 100° C. for 40 min. Upon completion the reaction solution was poured into water and the precipitate filtered. The collected solid was successively washed with water and small amount of ethanol and dried in-vacuo to obtain a solid. This solid was further purified by silica gel chromatography (2 to 5% gradient of MeOH in chloroform). The fractions were collected and concentrated in-vacuo to afford the title compound (27 mg, 0.066 mmol, 19.48% yield) as a white solid. 1H NMR (400 MHz, DMSO-d4, D2O) δ ppm 0.55 (m, 1H) 0.78-0.92 (m, 1H) 1.01-1.11 (m, 1H) 1.12-1.24 (m, 2H) 1.45 (s, 3H) 2.65 (s, 3H) 2.78 (s, 1H) 3.26-3.40 (m, 1H) 3.55 (m, 1H) 3.70 (d, J=11.6 Hz, 1H) 3.93 (d, J=11.4 Hz, 1 H) 4.02 (m, 1H) 4.30-4.39 (m, 1H) 7.54 (d, J=8.8 Hz, 2H) 8.08-8.16 (d, J=8.8 Hz, 2H) 8.20 (s, 1H). MS [M+H] found 409.

Workup

  1. customA microwave vial equipped with a magnetic stirrer
  2. customThe reaction was irradiated in the microwave at 100° C. for 40 min
  3. filtrationthe precipitate filtered
  4. washThe collected solid was successively washed with water and small amount of ethanol
  5. customdried in-vacuo
  6. customto obtain a solid
  7. customThis solid was further purified by silica gel chromatography (2 to 5% gradient of MeOH in chloroform)
  8. customThe fractions were collected
  9. concentrationconcentrated in-vacuo

Sources & evidence

ORD record
ord-5fee3de1113b46bd9f92146278ab3fff
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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