Sodium Bicarbonate → N-(5-(4-(cyclohexylthio)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfon-amide

HRID 1485564Notes

Reaction equation

HRID 1485564 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([S:12][CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:10]=2[N:11]=1.Cl[C:20]1[CH:25]=[C:24](Cl)[CH:23]=[CH:22][C:21]=1[S:27]([NH:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35](C2C=CC3N=CN=C(OC4CCOCC4)C=3N=2)[CH:36]=1)(=[O:29])=[O:28].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>[CH:13]1([S:12][C:9]2[C:10]3[N:11]=[C:2]([C:35]4[CH:36]=[C:31]([NH:30][S:27]([C:21]5[CH:20]=[CH:25][CH:24]=[CH:23][CH:22]=5)(=[O:28])=[O:29])[CH:32]=[N:33][CH:34]=4)[CH:3]=[CH:4][C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 665582972,4-dichloro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide2×HCID 866710706-Chloro-4-(cyclohexylthio)pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558381N-(5-(4-(cyclohexylthio)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfon-amideYield 89%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-4-(cyclohexylthio)pyrido[3,2-d]pyrimidine (Intermediate 15) (0.12 g, 0.429 mmol), N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (Intermediate 2) (0.12 g, 0.429 mmol), 1 N aq. sodium bicarbonate (0.858 ml, 0.858 mmol) and PdCl2(dppf)-CH2Cl2 (0.035 g, 0.043 mmol) in dioxane (2.14 ml) was subjected to microwave irradiation for 1 hour at 110° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with DCM. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give N-(5-(4-(cyclohexylthio)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfon-amide (0.09 g, 89%) as a brown solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.26-1.28 (1H, m), 1.34-1.43 (1H, m), 1.52-1.85 (4H, m), 1.85-1.87 (2H, m), 2.19-2.23 (2H, m), 4.12-4.19 (1H, m), 7.48-7.58 (3H, m), 7.92 (2H, d, J=8.8 Hz), 8.21 (1H, d, J=8.8 Hz), 8.32 (1H, d, J=9.2 Hz), 8.41-8.43 (2H, m), 8.99 (1H, s), 9.13 (1H, s). m/z=478.1 [M+1]+.

Workup

  1. customirradiation for 1 hour at 110° C.
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with DCM
  4. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Sources & evidence

ORD record
ord-2d27942612b145d18711c60fce14da16
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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