Sodium Bicarbonate → HCID 50915115, compound

HRID 2386216Notes

Reaction equation

HRID 2386216 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([CH3:21])[CH2:17][O:18][CH2:19][CH2:20][N:5]3[C:4]=2[N:3]=1.[CH3:22][NH:23][C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1)=[O:25].C([O-])(O)=O.[Na+].O.C(#N)C>O.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].CC(O)=O.O1CCOCC1>[CH:13]1([CH2:12][N:8]2[C:7](=[O:16])[C:6]3([CH3:21])[CH2:17][O:18][CH2:19][CH2:20][N:5]3[C:4]3[N:3]=[C:2]([C:30]4[CH:29]=[CH:28][C:27]([NH:26][C:24]([NH:23][CH3:22])=[O:25])=[CH:32][CH:31]=4)[N:11]=[CH:10][C:9]2=3)[CH2:15][CH2:14]1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 18373917Acetonitrile--water (1/1)HCID 86651562HCID 86651562, compound

Product 1

HCID 50915115HCID 50915115, compoundYield 44.9%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a microwave vial equipped with a magnetic stirrer was added 2-chloro-5-(cyclopropylmethyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (88 mg, 0.285 mmol), 1,4-dioxane (2 ml), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (118 mg, 0.428 mmol), NaHCO3 (saturated, 0.491 mL), and PdCl2(dppf) (209 mg, 0.285 mmol). The reaction was irradiated in the microwave at 100° C. for 40 min. The reaction solution was then poured into water, extracted with ethyl acetate three times and the combined organic layers were washed with water and then brine, then dried with Na2SO4, filtered, and the filtrate concentrated in-vacuo to give a brown residue. The aqueous layer was acidified with AcOH (pH about 5) and concentrated in-vacuo to give a grey residue. The combined residues were purified via preparative LC/MS (45-50% gradient of 10 mmol NH4HCO3 in 20/80(v/v) water/acetonitrile in 10 mmol NH4HCO3 in water, Phenomenex Gemini 5 μm C18, 75×30 mm column to give the title compound (54 mg, 0.128 mmol, 44.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.25-0.57 (m, 4H) 1.18 (m, 1H) 1.35 (s, 3H) 2.62-2.71 (m, 3H) 3.17-3.26 (m, 1H) 3.54-3.65 (m, 1H) 3.68 (d, J=11.62 Hz, 1H) 3.81 (dd, J=14.53, 6.95 Hz, 1H) 3.89-4.02 (m, 2H) 4.07 (dd, J=11.62, 3.54 Hz, 1H) 4.20 (dd, J=13.77, 2.40 Hz, 1H) 6.07 (d, J=4.80 Hz, 1H) 7.49 (d, J=8.84 Hz, 2H) 8.19 (d, J=8.84 Hz, 2 H) 8.36 (s, 1H) 8.72 (s, 1H). MS [M+H] found 423.

Workup

  1. customTo a microwave vial equipped with a magnetic stirrer
  2. customThe reaction was irradiated in the microwave at 100° C. for 40 min
  3. extractionextracted with ethyl acetate three times
  4. washthe combined organic layers were washed with water
  5. dry with materialbrine, then dried with Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated in-vacuo
  8. customto give a brown residue
  9. concentrationconcentrated in-vacuo
  10. customto give a grey residue

Sources & evidence

ORD record
ord-9bd79cb9215548fd98b9bcb663e277ad
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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