p-Toluenesulfonic acid → HCID 13520534, compound

HRID 485328Notes

Reaction equation

HRID 485328 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]=[CH:43]OC)=[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]([C:54]([F:57])([F:56])[F:55])[C:51]([S:58]([NH2:61])(=[O:60])=[O:59])=[CH:50][C:49]=1[S:62]([NH2:65])(=[O:64])=[O:63].C1(OC)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(#N)C>[NH2:61][S:58]([C:51]1[C:52]([C:54]([F:56])([F:57])[F:55])=[CH:53][C:48]2[NH:47][CH:43]([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)[NH:65][S:62](=[O:63])(=[O:64])[C:49]=2[CH:50]=1)(=[O:59])=[O:60]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7519AnisoleHCID 695612,4-Disulfamyl-5-trifluoromethylanilineHCID 131714304HCID 131714304, compound

Product 1

HCID 13520534HCID 13520534, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a mixture of (S)-1-[(S)-3-(benzoylthio)-2-methyl-1-oxopropyl]-4-[4-(2-methoxyethenyl)phenoxy]-L-proline, diphenylmethyl ester (3.6 g., 5.66 mmole), 4-amino-6-(trifluoromethyl)-1,3-benzenedisulfonamide (1.8 g., 5.7 mmole) and anisole (3.5 ml.) in 80 ml. of acetonitrile is added 120 mg. of p-toluenesulfonic acid. The reaction is essentially complete after refluxing for one hour. The solvent is removed under vacuum and the residue is triturated with diethyl ether to give a solid. The solid is purified by chromatography on an LPS-1 column eluted with ethyl acetate:pyridine:acetic acid:water (2400:50:15:27). After removal of the solvents on a rotary film evaporator using benzene to azeotrope off the acetic acid and pyridine, 3.8 g. of a homogeneous solid is obtained. Approximately half this material is passed through an LH-20 column (methanol) to give an analytically pure sample of (S)-4-[4-[[7-(aminosulfonyl)-3,4-dihydro-1,1-dioxo-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazin-3-yl]methyl]phenoxy]-1-[(S)-3-(benzoylthio)-2-methyl-1-oxopropyl]-L-proline; m.p. 170°-182° (foams); [α]D =-24.6° (c=1.0%, methanol). TLC (silica, methylene chloride:methanol:acetic acid; 8:1:1) Rf =0.47.

Workup

  1. temperatureafter refluxing for one hour
  2. customThe solvent is removed under vacuum
  3. customthe residue is triturated with diethyl ether
  4. customto give a solid
  5. customThe solid is purified by chromatography on an LPS-1 column
  6. washeluted with ethyl acetate:pyridine:acetic acid:water (2400:50:15:27)
  7. customAfter removal of the solvents
  8. customon a rotary film evaporator
  9. customof a homogeneous solid is obtained

Sources & evidence

ORD record
ord-fccc9b0de2d94e36b9ad7c635729e351
Source dataset
uspto-grants-1985_08
Patent number
US04536501

Reaction notes

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