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

HRID 1485567Notes

Reaction equation

HRID 1485567 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[CH2:16][CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[Cl:17][C:18]1[C:23]([NH:24][S:25]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])(=[O:27])=[O:26])=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][N:19]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:17][C:18]1[C:23]([NH:24][S:25]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])(=[O:27])=[O:26])=[CH:22][C:21]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][CH:13]4[CH2:16][CH2:15][CH2:14]4)[C:10]=3[N:11]=2)=[CH:20][N:19]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 866710746-chloro-N-cyclobutyl-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 66558385N-(2-chloro-5-(4-(cyclobutylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamideYield 81.2%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-N-cyclobutylpyrido[3,2-d]pyrimidin-4-amine (Intermediate 19) (0.050 g, 0.213 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.110 g, 0.256 mmol), PdCl2(dppf)-CH2Cl2 Adduct (1.74 mg, 2.13 μmol) and 1 N aq. sodium bicarbonate (0.426 ml, 0.426 mmol) in dioxane (1.00 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-(cyclobutylamino)pyrido[3,2-d]pyrimidin-6-yl) pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.087 g, 81%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.84-1.95 (2H, m), 2.10-2.20 (2H, m), 2.54-2.62 (2H, m), 4.77-4.87 (1H, m), 6.94-7.02 (2H, m), 7.34 (1H, d, J=8.0 Hz), 7.86-7.92 (1H, m), 8.07 (1H, d, J=8.8 Hz), 8.21 (1H, d, J=8.8 Hz), 8.65 (1H, s), 8.73 (1H, d, J=2.4 Hz), 8.84 (1H, d, J=2.4 Hz). m/z=503.2 [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-e50220fea7bf4f4fb2607dee183209ae
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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