Sodium Bicarbonate → HCID 66558206, compound

HRID 1182968Notes

Reaction equation

HRID 1182968 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16](B3OC(C)(C)C(C)(C)O3)[CH:17]=2)(=[O:10])=[O:9])=[C:4]([Cl:27])[CH:3]=1.Cl[C:29]1[CH:30]=[CH:31][C:32]2[N:33]=[CH:34][N:35]=[C:36]([O:39][CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[C:37]=2[N:38]=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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([C:29]3[CH:30]=[CH:31][C:32]4[N:33]=[CH:34][N:35]=[C:36]([O:39][CH:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)[C:37]=4[N:38]=3)[CH:17]=2)(=[O:9])=[O:10])=[C:4]([Cl:27])[CH:3]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 682287834-Bromo-2-chloro-N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]benzenesulfonamide2×HCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558206HCID 66558206, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-bromo-2-chloro-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (Intermediate 10) (0.0740 g, 0.279 mmol), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.145 g, 0.306 mmol), 1N aq. sodium bicarbonate (0.557 ml, 0.557 mmol) and PdCl2(dppf)-CH2Cl2 (0.0230 g, 0.0280 mmol) in dioxane (1.40 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 combined organic layers were washed brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give 4-bromo-2-chloro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (0.032 g, 20%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.04-2.12 (2H, m), 2.23-2.27 (2H, m), 3.68-3.74 (2H, m), 4.10-4.15 (2H, m), 5.63-5.69 (1H, m), 7.83 (1H, t, J=2.2 Hz), 7.92 (1H, brs), 8.13-8.16 (1H, m), 8.22 (1H, d, J=8.0 Hz), 8.34-8.42 (4H, m), 8.84 (1H, s). m/z=577.9 [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. washThe combined organic layers were washed brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Sources & evidence

ORD record
ord-92a42581cb3d47cf963787ba328743f0
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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