p-Toluenesulfonic acid monohydrate → N-(4-bromo-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine

HRID 1842791Notes

Reaction equation

HRID 1842791 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Br:29][C:30]1[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][C:33]([NH2:34])=[C:32]([O:40][CH3:41])[CH:31]=1>CC(O)CCC>[Br:29][C:30]1[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][C:33]([NH:34][C:2]2[N:7]=[C:6]([C:8]3[CH:9]=[N:10][N:11]4[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)=[C:32]([O:40][CH3:41])[CH:31]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 717431004-Bromo-2-methoxy-5-nitroaniline2×HCID 866773443-(2-Chloropyrimidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine2×

Product 1

HCID 71240843N-(4-bromo-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amineYield 59%

Reagents, catalysts & solvents 1

HCID 223862-PentanolSolvent

Procedure

A solution of 3-(2-chloropyrimidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (Intermediate 128, 0.893 g, 3.80 mmol), p-toluene sulphonic acid monohydrate (1.034 g, 5.43 mmol) and 4-bromo-2-methoxy-5-nitroaniline (Intermediate 4, 0.895 g, 3.62 mmol) in 2-pentanol (35 mL) was heated at reflux for 16 h under an atmosphere of N2. The mixture was then allowed to cool, and was concentrated in vacuo. The resulting residue was triturated in CH3CN until a yellow precipitate formed. The solid was collected by filtration and was washed with diethyl ether. The solid then was dissolved in 10% CH3OH in CH2Cl2 and the resulting solution was washed twice with sat. NaHCO3, then with water. The solution was then dried (MgSO4) and concentrated in vacuo. The resulting residue was triturated with CH3CN, the resulting solid collected by filtration, washed with diethyl ether, and then air dried to give the title compound (0.946 g, 59%) as a yellow solid; 1H NMR: 1.80-1.87 (2H, m), 1.96-2.03 (2H, m), 3.11 (2H, t), 4.04 (3H, s), 4.13 (2H, t), 7.17 (1H, d), 7.50 (1H, s), 8.13 (1H, s), 8.21 (1H, s), 8.45 (1H, d), 9.10 (1H, s); m/z: ES+ MH+ 445/447.

Workup

  1. temperatureat reflux for 16 h under an atmosphere of N2
  2. temperatureto cool
  3. concentrationwas concentrated in vacuo
  4. customThe resulting residue was triturated in CH3CN until a yellow precipitate
  5. customformed
  6. filtrationThe solid was collected by filtration
  7. washwas washed with diethyl ether
  8. dissolutionThe solid then was dissolved in 10% CH3OH in CH2Cl2
  9. washthe resulting solution was washed twice with sat. NaHCO3
  10. dry with materialThe solution was then dried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customThe resulting residue was triturated with CH3CN
  13. filtrationthe resulting solid collected by filtration
  14. washwashed with diethyl ether
  15. customair dried

Sources & evidence

ORD record
ord-76c8cc20f06a4834ae081a192036096b
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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