p-Toluenesulfonic acid → HCID 13520528, compound

HRID 485329Notes

Reaction equation

HRID 485329 reaction equation
[C:1]([S:9][CH2:10][C@@H:11]([CH3:46])[C:12]([N:14]1[CH2:34][CH:33]([O:35][C:36]2[CH:41]=[CH:40][C:39]([CH:42]=COC)=[CH:38][CH:37]=2)[CH2:32][C@H:15]1[C:16]([O:18]C(C1C=CC=CC=1)C1C=CC=CC=1)=[O:17])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:47][C:48]1[CH:53]=[C:52]([Cl:54])[C:51]([S:55]([NH2:58])(=[O:57])=[O:56])=[CH:50][C:49]=1[S:59]([NH:62][CH3:63])(=[O:61])=[O:60].[C:64]1(OC)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(#N)C>[NH2:58][S:55]([C:51]1[C:52]([Cl:54])=[CH:53][C:48]2[NH:47][CH:63]([CH2:42][C:39]3[CH:38]=[CH:37][C:36]([O:35][CH:33]4[CH2:34][N:14]([C:12](=[O:13])[C@H:11]([CH3:46])[CH2:10][S:9][C:1](=[O:8])[C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[C@H:15]([C:16]([OH:18])=[O:17])[CH2:32]4)=[CH:41][CH:40]=3)[N:62]([CH3:64])[S:59](=[O:61])(=[O:60])[C:49]=2[CH:50]=1)(=[O:56])=[O:57]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7519AnisoleHCID 518797METHYCLOTHIAZIDE RELATED COMPOUND A (100 MG) (4-AMINO-6-CHLORO-N-3-METHYL-M-BEN-ZENEDISULFONAMIDE)HCID 131714304HCID 131714304, compound

Product 1

HCID 13520528HCID 13520528, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (S)-1-[(S)-3-(benzoylthio)-2-methyl-1-oxopropyl]-4-[4-(2-methoxyethenyl)phenoxy]-L-proline, diphenylmethyl ester (4.0 g., 6.3 mmole), 4-amino-6-chloro-N3 -methyl-1,3-benzenedisulfonamide (1.89 g., 1 eq.), 4 ml. anisole, and 130 mg. p-toluenesulfonic acid in 200 ml. of acetonitrile is refluxed. 80 ml. of acetonitrile is distilled off in order to azeotrope off water. The reaction appears to be complete as soon as the distillation is finished. The reaction solution is evaporated and the residue is triturated with diethyl ether. The solid is flash chromatographed on LPS-1 silica eluting with ethyl acetate:acetone (1:1) followed by 10% acetic acid:acetone. After concentrating to a residue, water is added and the gummy solid is absorbed on a filter pad and washed with water to remove acetic acid. The product is then washed from the pad with ethyl acetate. The ethyl acetate solution is washed with water, dried (Na2SO4), and concentrated to a residue (3 g.). A portion of this residue is run through an LH-20 (methanol) column to give an analytically pure sample of (S)-4-[4-[[7-(aminosulfonyl)-6-chloro-3,4-dihydro-2-methyl-1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl]methyl]phenoxy]-1-[(S)-3-(benzoylthio)-2-methyl-1-oxopropyl]-L-proline; m.p. 228° (decomposition); [α]D =-31.7° (c=1.0%, methanol). TLC (silica, methylene chloride:methanol:acetic acid, 8:1:1) Rf =0.52.

Workup

  1. distillationof acetonitrile is distilled off in order
  2. distillationsoon as the distillation
  3. customThe reaction solution is evaporated
  4. customthe residue is triturated with diethyl ether
  5. customchromatographed on LPS-1 silica eluting with ethyl acetate:acetone (1:1)
  6. concentrationAfter concentrating to a residue, water
  7. additionis added
  8. customthe gummy solid is absorbed on a filter pad
  9. washwashed with water
  10. customto remove acetic acid
  11. washThe product is then washed from the pad with ethyl acetate
  12. washThe ethyl acetate solution is washed with water
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated to a residue (3 g.)

Sources & evidence

ORD record
ord-263ebfeaf0934f5881e899fb1cd6eb9c
Source dataset
uspto-grants-1985_08
Patent number
US04536501

Reaction notes

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