Potassium Carbonate → HCID 86670149, compound

HRID 2169606Notes

Reaction equation

HRID 2169606 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH2:10][N:11]2[CH2:20][CH:19]3[CH2:21][O:22][CH2:23][CH2:24][N:18]3[C:17]3[N:16]=[C:15]([Cl:25])[N:14]=[CH:13][C:12]2=3)[CH:3]=1.[C:26](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1>O1CCOCC1.O.CCOC(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]>[Cl:25][C:15]1[N:14]=[CH:13][C:12]2[N:11]([CH2:10][C:4]3[CH:3]=[C:2]([CH3:26])[CH:9]=[CH:8][C:5]=3[C:6]#[N:7])[CH2:20][CH:19]3[CH2:21][O:22][CH2:23][CH2:24][N:18]3[C:17]=2[N:16]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86670150HCID 86670150, compound

Product 1

HCID 86670149HCID 86670149, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 20 mL vial were added 4-bromo-2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)benzonitrile (105 mg, 0.250 mmol), potassium carbonate (69.0 mg, 0.499 mmol), PdCl2(dppf) (18.26 mg, 0.025 mmol), and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (0.042 mL, 0.300 mmol) in dioxane (2 mL) and water (0.4 mL). The resulting brown suspension was stirred overnight at 100° C. The reaction mixture was subsequently diluted with EtOAc and washed with saturated NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The product was purified by flash chromatography (SiO2, 4 g column, 2:8 to 8:2 EtOAc/Hexane gradient) to give the title compound as a tan solid (52 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.33 (s, 3 H), 2.92-3.08 (m, 3 H), 3.10-3.20 (m, 2 H), 3.24-3.32 (m, 2 H), 3.40-3.52 (m, 2 H), 3.62-3.75 (m, 2 H), 3.81-3.90 (m, 2 H), 3.91-4.00 (m, 2 H), 4.21-4.31 (m, 2 H), 4.41-4.63 (m, 3 H), 7.30-7.38 (m, 2 H), 7.38-7.55 (m, 3 H), 7.67-7.73 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H18ClN5O, 356.1; found 356.1.

Workup

  1. washwashed with saturated NH4Cl (3×)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography (SiO2, 4 g column, 2:8 to 8:2 EtOAc/Hexane gradient)

Sources & evidence

ORD record
ord-6b4a381fccb643cc9e137f08e43c4c51
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

Loading…