Sodium Bicarbonate → HCID 58169829, compound

HRID 2386280Notes

Reaction equation

HRID 2386280 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]3[CH2:17][CH2:16][S:15](=[O:19])(=[O:18])[CH2:14][CH2:13]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.[CH:26]1([NH:29][C:30]([NH:32][C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)=[O:31])[CH2:28][CH2:27]1.C([O-])(O)=O.[Na+]>O1CCOCC1.C1COCC1.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]>[CH:26]1([NH:29][C:30]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH:12]5[CH2:17][CH2:16][S:15](=[O:19])(=[O:18])[CH2:14][CH2:13]5)[C:7](=[O:20])[C:6]5([CH3:25])[CH2:21][O:22][CH2:23][CH2:24][N:5]5[C:4]=4[N:3]=3)=[CH:35][CH:34]=2)=[O:31])[CH2:28][CH2:27]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 86651597HCID 86651597, compound

Product 1

HCID 58169829HCID 58169829, compoundYield 70.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-chloro-5-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-6a-methyl-6a,7,9,10-tetrahydro[1,4]oxazino[3,4-h]pteridin-6(5H)-one (6.50 mg, 0.017 mmol), 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (8.63 mg, 0.029 mmol), saturated aqueous NaHCO3 (0.75 ml) and PdCl2(dppf) (1.10 mg, 1.34 μmol) in 1,4-dioxane (1 ml) was irradiated in the microwave at 110° C. for 30 minutes The reaction mixture was diluted with THF and passed through 0.45 mM PTFE syringe filter (washed with small amount of THF). The filtrate was purified by preparative HPLC (eluting with a gradient of 15-40% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column). The fractions containing the desired product were combined and were evaporated under reduced pressure. Then NaHCO3 aqueous solution was added (in order to adjust the pH to basic) and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (6.2 mg, 0.012 mmol, 70% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) d ppm 0.36-0.45 (m, 2H) 0.59-0.69 (m, 2H) 1.32 (s, 3H) 1.93-2.17 (m, 2H) 2.51-2.60 (m, 1H) 2.85-3.76 (m, 9H) 3.91-3.99 (m, 1H) 4.01-4.10 (m, 1H) 4.14-4.25 (m, 1H) 4.45-4.62 (m, 1H) 6.58 (br. s., 1H) 7.49-7.56 (m, 2H) 8.16-8.24 (m, 2H) 8.49 (s, 1H) 8.75 (s, 1H). MS [M+H] found 527.

Workup

  1. customwas irradiated in the microwave at 110° C. for 30 minutes The reaction mixture
  2. custompassed through 0.45 mM PTFE syringe
  3. filtrationfilter
  4. wash(washed with small amount of THF)
  5. customThe filtrate was purified by preparative HPLC (
  6. washeluting with a gradient of 15-40% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)
  7. additionThe fractions containing the desired product
  8. customwere evaporated under reduced pressure
  9. additionThen NaHCO3 aqueous solution was added (in order
  10. extractionextracted with EtOAc
  11. dry with materialThe combined organic phases were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-047c313248ed42d0944fa87423ceb4a1
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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