p-Toluenesulfonic acid monohydrate → HCID 71240803, compound

HRID 1842670Notes

Reaction equation

HRID 1842670 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[C:5]([CH3:17])=[CH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:30][O:31][C:32]1[CH:38]=[C:37]([C:39]2[CH2:40][CH2:41][N:42]([CH3:45])[CH2:43][CH:44]=2)[C:36]([N+:46]([O-:48])=[O:47])=[CH:35][C:33]=1[NH2:34]>CC(O)CCC>[CH3:30][O:31][C:32]1[CH:38]=[C:37]([C:39]2[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH:40]=2)[C:36]([N+:46]([O-:48])=[O:47])=[CH:35][C:33]=1[NH:34][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[C:5]([CH3:17])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 59291169HCID 59291169, compound2×HCID 866773252-methoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitroaniline2×

Product 1

HCID 71240803HCID 71240803, compoundYield 63.2%

Reagents, catalysts & solvents 1

HCID 223862-PentanolSolvent

Procedure

A solution of 3-(2-chloro-5-methylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine (Intermediate 5, 271 mg, 1.00 mmol), p-toluene sulphonic acid monohydrate (271 mg, 1.43 mmol) and 2-methoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitroaniline (Intermediate 3, 250 mg, 0.95 mmol) were heated in 2-pentanol (12 mL) at reflux under N2 for 30 h. The mixture was then concentrated in vacuo and the residue was dissolved in CH3OH. Purification by ion exchange chromatography (SCX column), eluting with 7M methanolic ammonia, gave the title compound (283 mg, 63%) as an orange powder after trituration with CH3CN. 1H NMR: 2.28-2.36 (5H, m), 2.44 (3H, s), 2.60 (2H, t), 3.00 (2H, d), 4.00 (3H, d), 5.64 (1H, s), 6.97 (1H, s), 7.13 (1H, m), 7.40 (1H, m), 8.27 (1H, s), 8.39 (1H, s), 8.53 (1H, d), 8.61 (1H, s), 8.83 (1H, d), 8.87 (1H, s); m/z: ES− MH− 470.

Workup

  1. temperatureat reflux under N2 for 30 h
  2. concentrationThe mixture was then concentrated in vacuo
  3. dissolutionthe residue was dissolved in CH3OH
  4. customPurification by ion exchange chromatography (SCX column)
  5. washeluting with 7M methanolic ammonia

Sources & evidence

ORD record
ord-83286be2b328412288c55d6738a26a38
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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