2,6-Dichlorobenzenesulfonylchloride → HCID 44609705, compound

HRID 1963779Notes

Reaction equation

HRID 1963779 reaction equation
[Cl:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:37]=1[S:43](Cl)(=[O:45])=[O:44]>C1COCC1>[Cl:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:37]=1[S:43]([NH:8][C:7]1[C:2]([Cl:1])=[N:3][CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:6]=1)(=[O:45])=[O:44]

Participants

5

Reactant 3

HCID 5221832,6-DichlorobenzenesulfonylchlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 582294522-Chloro-5-[4-(4-morpholinyl)-6-quinolinyl]-3-pyridinamine

Product 1

HCID 44609705HCID 44609705, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(Some starting materials may be obtained from Alfa Aesar, Ward Hills, Mass.) To a flame-dry 50 mL rb flask was added 2-chloro-5-(4-morpholinoquinolin-6-yl)pyridin-3-amine (0.07 g, 0.2 mmol) and THF (8 mL). The reaction mixture was cooled to 0° C. followed by adding sodium bis(trimethylsilyl)amide, 1.0 m solution in tetrahydrofuran (0.4 mL, 0.4 mmol). After the addition, it was continued to stir at 0° C. under N2. After 30 min, 2,6-dichlorobenzene-1-sulfonyl chloride (0.07 g, 0.3 mmol) was added into the reaction mixture. After the addition, it was continued to stir at 0° C. then slowly warmed up to rt overnight. The reaction was quenched with water. The solvent was concentrated. The residue was partitioned between EtOAc/water. The organic layer was washed with brine, dried over MgSO4 and concentrated. The crude product was purified using SiO2 (12 g) chromatography with DCM:EtOAc:MeOH=70%:26%:4% as the solvent system to afford the desired product as light yellow solid (63.0 mg). MS (ESI pos. ion) m/z: calc'd for C24H19Cl3N4O3S: 548.1; found: 549.4 (M+1). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.21-3.38 (m, 4 H) 3.93-4.11 (m, 4 H) 6.94 (d, J=4.97 Hz, 1 H) 7.33-7.44 (m, 1 H) 7.45-7.55 (m, 2 H) 7.85 (dd, J=8.77, 2.05 Hz, 1 H) 8.18 (d, J=8.77 Hz, 1 H) 8.25 (d, J=1.90 Hz, 1 H) 8.39-8.50 (m, 2 H) 8.81 (d, J=4.97 Hz, 1 H).

Workup

  1. additionAfter the addition, it
  2. additionAfter the addition, it
  3. stirringto stir at 0° C.
  4. temperaturethen slowly warmed up to rt overnight
  5. customThe reaction was quenched with water
  6. concentrationThe solvent was concentrated
  7. customThe residue was partitioned between EtOAc/water
  8. washThe organic layer was washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe crude product was purified

Sources & evidence

ORD record
ord-885a5acbd78b4f088a08df343c4885a3
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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