Sulfuryl chloride → HCID 11249869, compound

HRID 857440Notes

Reaction equation

HRID 857440 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[C:10](=[O:32])[NH:11][C:12]3[C:17]([C:18]=2[C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=2[O:26]C)=[CH:16][C:15]([C:28]([F:31])([F:30])[F:29])=[CH:14][CH:13]=3)=[CH:4][CH:3]=1.N[C:34]1C=CC(SC2C(=O)NC3C(C=2C2C=C(Cl)C=CC=2O)=CC(C(F)(F)F)=CC=3)=C[CH:35]=1.[S:64](Cl)(Cl)(=[O:66])=[O:65]>N1C=CC=CC=1.C(Cl)Cl>[Cl:25][C:23]1[CH:22]=[CH:21][C:20]([OH:26])=[C:19]([C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:28]([F:30])([F:31])[F:29])[CH:16]=3)[NH:11][C:10](=[O:32])[C:9]=2[S:8][C:5]2[CH:4]=[CH:3][C:2]([NH:1][S:64]([CH2:34][CH3:35])(=[O:66])=[O:65])=[CH:7][CH:6]=2)[CH:24]=1

Participants

6

Reactant 3

HCID 24648Sulfuryl chlorideHCID 11385708HCID 11385708, compoundHCID 21868814HCID 21868814, compound

Product 1

HCID 11249869HCID 11249869, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(4-Amino-phenylsulfanyl)-4-(5-chloro-2-methoxy-phenyl)-6-trifluoromethyl-1H-quinolin-2-one or 3-(4-Amino-phenylsulfanyl)-4-(5-chloro-2-hydroxy-phenyl)-6-trifluoromethyl-1H-quinolin-2-one (49.0 mg, 103 μmol, 1 eq) in pyridine (50 μL) and methylene chloride (500 μL) was added the appropriate sulfonyl chloride (422 μmol, 4.1 eq), and the mixture stirred overnight at room temperature, or at 80° C. in the absense of methylene chloride for difficult cases. The pyridine was removed in vacuo, and 4 N NaOH was added. The suspension was diluted with water, washed with chloroform, and adjusted to pH 5 with 1 M HCl. The product was extracted into a mixture of EtOAc and methylene chloride, dried with Magnesium sulfate, and concentrated in vacuo. Final purification was effected by reverse phase HPLC to afford pure Ib. 1H NMR (300 MHz, CDCl3) δ 11.04 (s, 1H), 8.90 (s, 1H), 7.67 (d, J=8.6 Hz, 1H), 7.43 (s, 1H), 7.40–7.30 (m, 2H), 7.30–7.24 (m, 3H), 7.11 (d, J=2.5 Hz, 1H), 6.98 (d, J=8.7 Hz, 1H), 6.91 (d, J=8.7 Hz, 2H), 2.99 (q, J=7.4 Hz, 2H), 1.21 (t, J=7.4 Hz, 3H); LCMS (M+H) 555, RT=3.177 (Method 1).

Workup

  1. customat 80° C.
  2. customThe pyridine was removed in vacuo, and 4 N NaOH
  3. additionwas added
  4. additionThe suspension was diluted with water
  5. washwashed with chloroform
  6. extractionThe product was extracted into a mixture of EtOAc and methylene chloride
  7. dry with materialdried with Magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customFinal purification
  10. customto afford pure Ib
  11. customLCMS (M+H) 555, RT=3.177 (Method 1)

Sources & evidence

ORD record
ord-c4c4d3b92afd4193bc17319d5ecdce69
Source dataset
uspto-grants-2006_12
Patent number
US07145013B2

Reaction notes

Loading…