Sodium Bicarbonate → N-(2-chloro-5-(4-(3,5-dimethylisoxazol-4-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide

HRID 1485569Notes

Reaction equation

HRID 1485569 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:12][C:13]3[C:14]([CH3:19])=[N:15][O:16][C:17]=3[CH3:18])[C:10]=2[N:11]=1.[Cl:20][C:21]1[C:26]([NH:27][S:28]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=2[F:38])(=[O:30])=[O:29])=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][N:22]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:20][C:21]1[C:26]([NH:27][S:28]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=2[F:38])(=[O:30])=[O:29])=[CH:25][C:24]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][C:13]4[C:14]([CH3:19])=[N:15][O:16][C:17]=4[CH3:18])[C:10]=3[N:11]=2)=[CH:23][N:22]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 866710766-chloro-N-(3,5-dimethyl-4-isoxazolyl)-Pyrido[3,2-d]pyrimidin-4-amine2×HCID 86671080N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide2×

Product 1

HCID 66558473N-(2-chloro-5-(4-(3,5-dimethylisoxazol-4-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamideYield 27%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-(6-chloropyrido[3,2-d]pyrimidin-4-yl)-3,5-dimethylisoxazol-4-amine (Intermediate 21) (0.040 g, 0.145 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.069 g, 0.160 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.012 g, 0.015 μmol) and 1 N aq. sodium bicarbonate (0.290 ml, 0.290 mmol) in dioxane (1.40 ml) subjected to microwave irradiation for 1 hour at 110° C. After cooling to room temperature, the reaction mixture was filtered through Celite and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give N-(2-chloro-5-(4-(3,5-dimethylisoxazol-4-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.021 g, 27%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.30 (3H, s), 2.45 (3H, s), 6.89-7.05 (2H, m), 7.27 (1H, s), 7.79-7.92 (1H, m), 8.20 (1H, d, J=8.8 Hz), 8.26 (1H, s), 8.36 (1H, d, J=8.8 Hz), 8.73 (1H, s), 8.76 (1H, s), 8.89 (1H, s). m/z=544.1 [M+1]+.

Workup

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

Sources & evidence

ORD record
ord-a4d51b14cbc141fba47a7f8f455314b0
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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