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

HRID 1182976Notes

Reaction equation

HRID 1182976 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:12][CH:13]3[CH2:18][CH2:17]O[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[Cl:19][C:20]1[C:25]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])(=[O:29])=[O:28])=[CH:24][C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:19][C:20]1[C:25]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])(=[O:29])=[O:28])=[CH:24][C:23]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][CH:13]4[CH2:18][CH2:17][CH2:15][CH2:14]4)[C:10]=3[N:11]=2)=[CH:22][N:21]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 866710726-chloro-N-(tetrahydro-2H-pyran-4-yl)-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 66558384N-(2-chloro-5-(4-(cyclo pentyl amino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamideYield 52%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-N-(tetrahydro-2H-pyran-4-yl)pyrido[3,2-d]pyrimidin-4-amine (Intermediate 18) (0.043 g, 0.173 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.089 g, 0.207 mmol), PdCl2(dppf)-CH2Cl2Adduct (1.41 mg, 1.73 μmol) and 1 N aq. sodium bicarbonate (0.346 ml, 0.346 mmol) in dioxane (0.864 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-(cyclo pentyl amino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.046 g, 52%) as a white solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.65-1.89 (6H, m), 2.18-2.25 (2H, m), 4.61-4.66 (1H, m), 6.93-7.01 (2H, m), 7.22 (1H, d, J=7.6 Hz), 7.85-7.90 (1H, m), 8.07 (1H, d, J=8.8 Hz), 8.21 (1H, d, J=8.8 Hz), 8.66 (1H, s), 8.74 (1H, d, J=2.0 Hz), 8.82 (1H, d, J=2.0 Hz). m/z=517.2 [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-5608cd4a833a4c0e8da9f7a96d33969e
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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