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

HRID 1485546Notes

Reaction equation

HRID 1485546 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])(=[O:18])=[O:17])[CH:12]=[N:13][CH:14]=2)O1.Cl[C:29]1[CH:30]=[CH:31][C:32]2[N:33]=[CH:34][N:35]=[C:36]([O:39][CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[C:37]=2[N:38]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[O:43]1[CH2:42][CH2:41][CH:40]([O:39][C:36]2[C:37]3[N:38]=[C:29]([C:9]4[CH:10]=[C:11]([NH:15][S:16]([C:19]5[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=5[F:26])(=[O:17])=[O:18])[CH:12]=[N:13][CH:14]=4)[CH:30]=[CH:31][C:32]=3[N:33]=[CH:34][N:35]=2)[CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 574165052,4-Difluoro-N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzene-1-sulfonamide2×HCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558031N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamideYield 108%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluoro benzenesulfonamide (0.110 g, 0.278 mmol) (Intermediate 4), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.081 g, 0.305 mmol), 1 N aq. sodium bicarbonate (0.555 ml, 0.555 mmol) and PdCl2(dppf)-CH2Cl2Adduct (23.0 mg, 2.80 μmol) in dioxane (2.78 ml) was subjected to microwave irradiation for 1 hour at 110° C. The reaction mixture was cooled to room temperature, filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1) to give N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.15 g, 18%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 1.78-1.98 (2H, m), 2.12-2.26 (2H, m), 3.55-3.72 (2H, m), 3.90-4.05 (2H, m), 5.58-5.72 (1H, m), 7.20-7.42 (1H, m), 7.48-7.62 (2H, m), 7.90-8.05 (1H, m), 8.36-8.52 (2H, m), 8.58 (1H, d, J=8.2 Hz), 8.86 (1H, s), 9.13 (1H, s), 11.29 (1H, br s). m/z=500.1 [M+1]+.

Workup

  1. customirradiation for 1 hour at 110° C
  2. filtrationfiltered through a Celite pad
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1)

Sources & evidence

ORD record
ord-cf91fcebbed54012a1f841505c048cec
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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