p-Toluenesulfonic acid monohydrate → HCID 71239353, compound

HRID 1842677Notes

Reaction equation

HRID 1842677 reaction equation
[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]3[C:24]([Cl:25])=[CH:23][N:22]=[C:21](Cl)[N:20]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:39][O:40][C:41]1[CH:47]=[C:46]([C:48]2[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH:53]=2)[C:45]([N+:55]([O-:57])=[O:56])=[CH:44][C:42]=1[NH2:43]>CC(O)CCC>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]3[C:24]([Cl:25])=[CH:23][N:22]=[C:21]([NH:43][C:42]4[CH:44]=[C:45]([N+:55]([O-:57])=[O:56])[C:46]([C:48]5[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH:49]=5)=[CH:47][C:41]=4[O:40][CH3:39])[N:20]=3)=[CH:11]2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 707007943-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole2×HCID 866773252-methoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitroaniline2×

Product 1

HCID 71239353HCID 71239353, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 223862-PentanolSolvent

Procedure

A mixture of 1-(benzenesulfonyl)-3-(2,5-dichloropyrimidin-4-yl)indole (Intermediate 10, 384 mg, 0.95 mmol), p-toluene sulphonic acid monohydrate (271 mg, 1.43 mmol) and 2-s methoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitroaniline (Intermediate 3, 250 mg, 0.95 mmol) was heated in 2-pentanol (12 mL) at reflux under N2 for 24 h. Further p-toluene sulphonic acid monohydrate (0.090 g, 0.48 mmol) was then added and the mixture was heated at reflux for a further 6 h. The mixture was then concentrated in vacuo and the resulting reside was dissolved into a mixture of CH2Cl2, CH3OH and EtOAc (10 mL, 3 mL and 3 mL). This solution was concentrated in vacuo onto silica. Purification by FCC, eluting with 4-10% CH3OH in CH2Cl2 gave the title compound (415 mg, 56%) as a yellow foam; 1H NMR: 2.29 (1.95H, s), 2.52 (0.7H, m), 2.73 (2.6H, s), 3.18 (1.4H, m), 3.57 (2H, s), 3.96 (3H, s), 5.68 (1H, s), 7.00 (1H, s), 7.11 (1.3H, d), 7.26 (1H, m), 7.44 (1H, m), 7.49 (1.3H, d), 7.64 (2H, t), 7.73 (1H, m), 8.01 (1H, d), 8.07-8.15 (2H, m), 8.19 (1H, d), 8.64 (2H, d), 8.70 (1H, s), 8.97 (1H, s); (the spectrum seems to appear to show a mixture of rotamers, arising due to restricted rotation of bonds within the molecule) m/z: ES+ MH+ 631.

Workup

  1. temperatureat reflux under N2 for 24 h
  2. temperaturethe mixture was heated
  3. temperatureat reflux for a further 6 h
  4. concentrationThe mixture was then concentrated in vacuo
  5. dissolutionthe resulting reside was dissolved into a mixture of CH2Cl2, CH3OH and EtOAc (10 mL, 3 mL and 3 mL)
  6. concentrationThis solution was concentrated in vacuo onto silica
  7. customPurification by FCC
  8. washeluting with 4-10% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-33f10eba04344c148857a2463bd64093
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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