Sodium Bicarbonate → N-(5-(4-(pyridin-3-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide

HRID 1485553Notes

Reaction equation

HRID 1485553 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]([NH:33][S:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)(=[O:36])=[O:35])[CH:30]=[N:31][CH:32]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([O:12][C:9]2[C:10]3[N:11]=[C:2]([C:27]4[CH:28]=[C:29]([NH:33][S:34]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=5)(=[O:35])=[O:36])[CH:30]=[N:31][CH:32]=4)[CH:3]=[CH:4][C:5]=3[N:6]=[CH:7][N:8]=2)[CH:14]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 52936632N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide2×HCID 866710686-chloro-4-(3-pyridinyloxy)-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558114N-(5-(4-(pyridin-3-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamideYield 125.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-4-(pyridin-3-yloxy)pyrido[3,2-d]pyrimidine (0.090 g, 0.348 mmol) (Intermediate 8), N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (0.150 g, 0.418 mmol) (Intermediate 2), PdCl2(dppf)-CH2Cl2Adduct (0.057 g, 0.070 mmol) and 1N aq. sodium bicarbonate (0.70 ml, 0.70 mmol) in dioxane (1.74 ml) was subjected to microwave irradiation for 30 min at 120° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with EtOAc. The filtrate was diluted water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (EtOAc only) to give N-(5-(4-(pyridin-3-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (0.20 g, 13%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 7.45-7.49 (2H, m), 7.51-7.56 (1H, m), 7.61 (1H, dd, J=8.4 and 4.8 Hz), 7.84-7.87 (2H, m), 7.92-7.95 (1H, m), 8.38 (1H, d, J=2.8 Hz), 8.45 (1H, s), 8.49-8.51 (2H, m), 8.53 (1H, dd, J=4.8 and 1.2 Hz), 8.66 (1H, d, J=2.4 Hz), 8.73 (1H, s), 9.06 (1H, d, J=2.0 Hz). m/z=457 [M+1]+.

Workup

  1. customirradiation for 30 min at 120° C.
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with EtOAc
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography on SiO2 (EtOAc only)

Sources & evidence

ORD record
ord-ec11bdff181d4bdeacb174ef3e520dbe
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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