Benzenesulfonyl chloride → HCID 66558205, compound

HRID 1485554Notes

Reaction equation

HRID 1485554 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[C:9]3[N:17]=[C:16]([C:18]4[N:23]=[C:22]([NH2:24])[CH:21]=[N:20][CH:19]=4)[CH:15]=[CH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:3][CH2:2]1.[C:25]1([S:31](Cl)(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>N1C=CC=CC=1.C(Cl)Cl>[O:1]1[CH2:2][CH2:3][CH:4]([O:7][C:8]2[C:9]3[N:17]=[C:16]([C:18]4[N:23]=[C:22]([NH:24][S:31]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)(=[O:33])=[O:32])[CH:21]=[N:20][CH:19]=4)[CH:15]=[CH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 7369Benzenesulfonyl chlorideHCID 68228541HCID 68228541, compound

Product 1

HCID 66558205HCID 66558205, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)-2-(N,N-bis(boc-amino))pyrazine (Intermediate 10) (0.845 g, 1.61 mmol) in DCM (8.05 ml) was slowly added TFA (2.48 ml, 32.2 mmol) at 0° C. After stirring for 4 hours at room temperature, the reaction mixture was quenched with 1N NaOH, and extracted with DCM. The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give 6-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyrazin-2-amine (0.27 g, 52%) as a yellow solid. To a solution of 6-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyrazin-2-amine (0.1 g, 0.308 mmol) in pyridine (1.542 ml) was slowly added benzenesulfonyl chloride (0.050 ml, 0.385 mmol) at 0° C. After stirring for 6 hours at room temperature, the reaction mixture was diluted with DCM and quenched with 1N aq. HCl. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was washed with EtOAc and the resulting solid was collected by filtration to give N-(6-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyrazin-2-yl)benzenesulfonamide (0.02 g, 14%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 1.82-1.90 (2H, m), 2.14-2.17 (2H, m), 3.57-3.62 (2H, m), 3.92-4.06 (2H, m), 5.59-5.63 (1H, m), 7.63-7.65 (3H, m), 8.10 (2H, dd, J=2.0, 7.6 Hz), 8.43 (1H, s), 8.49 (1H, d, J=8.8 Hz), 8.55 (1H, d, J=8.8 Hz), 8.89 (1H, s), 9.21 (1H, s), 11.96 (1H, s). m/z=465.0 [M+1]+.

Workup

  1. customat 0° C
  2. customquenched with 1N aq. HCl
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washThe residue was washed with EtOAc
  8. filtrationthe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-fd33f471433a467086af09447a35a99f
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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