Sodium Carbonate → HCID 86715516, compound

HRID 2284601Notes

Reaction equation

HRID 2284601 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][CH3:13])[C:10]=2[N:11]=1.[Cl:14][C:15]1[C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:18]=[CH:17][N:16]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[Cl:14][C:15]1[C:20]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([O:12][CH3:13])[C:10]=3[N:11]=2)=[CH:19][CH:18]=[CH:17][N:16]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 120670602-Chloropyridine-3-boronic acid pinacol esterHCID 86715513HCID 86715513, compound

Product 1

HCID 86715516HCID 86715516, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
98 °C

Procedure

A reaction flask was charged 6-chloro-4-methoxypyrido[3,2-d]pyrimidine (3.5 g, 17.8 mmol), 2-chloro-3-pyridineboronic acid pinacol ester (4.35 g, 18.2 mmol), Na2CO3 (4.0 g, 38.2 mmol) and 1,4-dioxane (100 mL) and a stir bar. The contents were degassed by vacuum and back filled with argon three times while stirring. Subsequently, Pd(PPh3)3 (0.87 g, 0.75 mmol) was added to the reaction contents, repeated degassing cycles and heated under argon at 98° C. The heating was stopped after overnight, the yellow hot heterogeneous reaction mixture was suction filtered on a Buchner funnel and washed the cake with additional amount of dioxane (30 mL). The pale yellow clear filtrate solution was passed through a pad of Celite® and concentrated the filtrate. The crude pale yellow solid residue was partitioned between CH2Cl2 (150 mL)/water (50 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The crude concentrate was stirred in EtOAc (30 mL) and suction filtered. The filter cake was washed further with EtOAc (10 mL) and dried to obtain 1.6 g of 6-(2-chloropyridin-3-yl)-4-methoxypyrido[3,2-d]pyrimidine (purity: 95%) as a white solid. The filtrate was concentrated and purified the concentrate by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g, 0-30-60% EtOAC/hexanes eluting solvent gradient) to obtain additional 0.65 g of titled compound. 1H NMR (300 MHz, DMSO-d6): δ 8.92 (s, 1H), 8.57 (dd, J=4.8, 2.0 Hz, 1H), 8.45 (d, J=8.7 Hz, 1H), 8.28 (d, J=8.7 Hz, 1H), 8.13 (dd, J=7.6, 2.0 Hz, 1H), 7.63 (dd, J=7.6, 4.8 Hz, 1H), 4.16 (s, 3H).

Workup

  1. customThe contents were degassed by vacuum
  2. additionback filled with argon three times
  3. customrepeated degassing cycles
  4. customthe yellow hot heterogeneous reaction mixture
  5. filtrationfiltered on a Buchner funnel
  6. washwashed the cake with additional amount of dioxane (30 mL)
  7. concentrationconcentrated the filtrate
  8. customThe crude pale yellow solid residue was partitioned between CH2Cl2 (150 mL)/water (50 mL)
  9. customThe organic layer was separated
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. concentrationThe crude concentrate
  14. stirringwas stirred in EtOAc (30 mL)
  15. filtrationsuction filtered
  16. washThe filter cake was washed further with EtOAc (10 mL)
  17. customdried

Sources & evidence

ORD record
ord-117522f602e2449483968b5e19bf7d4d
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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