Sodium Bicarbonate → HCID 66558030, compound

HRID 1182958Notes

Reaction equation

HRID 1182958 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]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>[O:16]1[CH2:17][CH2:18][CH: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)[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 52936632N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide2×HCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558030HCID 66558030, compoundYield 19.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (60.0 mg, 0.226 mmol) in 1,4-dioxane (1.20 mL) was added N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (Intermediate 2) (122 mg, 0.339 mmol), PdCl2(dppf)2CH2Cl2 (18.0 mg, 0.0230 mmol), and 1N aq. NaHCO3 (0.452 mL, 0.452 mmol) at room temperature. The reaction mixture 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 with 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 (Hex:EtOAc=3:1) to give N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (20.0 mg, 19%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.02-2.11 (2H, m), 2.23-2.27 (2H, m), 3.68-3.74 (2H, m), 4.10-4.15 (2H, m), 5.64-5.69 (1H, m), 7.07 (1H, brs), 7.47-7.51 (2H, m), 7.56-7.60 (1H, m), 7.85-7.88 (2H, m), 8.21 (1H, d, J=8.8 Hz), 8.36 (1H, d, J=8.8 Hz), 8.38 (1H, s), 8.43 (1H, t, J=2.2 Hz), 8.83 (1H, s), 9.16 (1H, s); m/z=464.2 [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. additionThe filtrate was diluted with water
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=3:1)

Sources & evidence

ORD record
ord-3c85e22c1f3543fdb23a0f727920d04b
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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