Sodium Bicarbonate → HCID 66558032, compound

HRID 1485547Notes

Reaction equation

HRID 1485547 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Cl[C:28]1[CH:29]=[CH:30][C:31]2[N:32]=[CH:33][N:34]=[C:35]([O:38][CH:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[C:36]=2[N:37]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)(=[O:10])=[O:11])=[CH:6][C:5]([C:28]2[CH:29]=[CH:30][C:31]3[N:32]=[CH:33][N:34]=[C:35]([O:38][CH:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[C:36]=3[N:37]=2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 57545850HCID 57545850, compound2×HCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558032HCID 66558032, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene sulfonamide (0.114 g, 0.290 mmol) (Intermediate 5), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.070 g, 0.263 mmol), 1 N aq. sodium bicarbonate (0.527 ml, 0.527 mmol) and PdCl2(dppf)-CH2Cl2Adduct (22.0 mg, 2.60 μmol) in dioxane (1.5 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-(2-chloro-5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (0.030 g, 23%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 1.75-1.98 (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), 7.50-7.70 (3H, m), 7.85 (1H, d, J=7.6 Hz), 8.45 (1H, d, J=8.4 Hz), 8.58-8.72 (2H, m), 8.87 (1H, s), 9.04 (1H, br s), 10.55 (1H, s). m/z=498.09 [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-3ded2a6ed2774df7bd2ad08e86615a0a
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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