Sodium Bicarbonate → HCID 66558475, compound

HRID 1182981Notes

Reaction equation

HRID 1182981 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[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[C:10]=2[N:11]=1.[Cl:24][C:25]1[C:30]([NH:31][S:32]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[F:42])(=[O:34])=[O:33])=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][N:26]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:24][C:25]1[C:30]([NH:31][S:32]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[F:42])(=[O:34])=[O:33])=[CH:29][C:28]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][C:13]4[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:21])[F:22])=[CH:15][CH:14]=4)[C:10]=3[N:11]=2)=[CH:27][N:26]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 86671078HCID 86671078, compound2×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 66558475HCID 66558475, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-N-(4-(trifluoromethoxy)phenyl)pyrido[3,2-d]pyrimidin-4-amine (Intermediate 23) (0.050 g, 0.147 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.070 g, 0.161 mmol), PdCl2(dppf)-CH2Cl2Adduct (5.99 mg, 7.34 μmol) and 1 N aq. sodium bicarbonate (0.294 ml, 0.294 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-(4-(trifluoromethoxy)phenylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.049 g, 55%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 6.88-7.05 (2H, m), 7.34 (2H, d, J=8.8 Hz), 7.85-7.95 (1H, m), 8.05-8.10 (2H, m), 8.19 (1H, d, J=8.8 Hz), 8.34 (1H, d, J=8.4 Hz), 8.84 (1H, s), 8.85-8.90 (2H, m), 9.26 (1H, br s). 1NH was not detected. m/z=609.1 [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-8ae374931950451b85740c684573e5a5
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

Loading…