2-Pentanol → N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842807Notes

Reaction equation

HRID 1842807 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)[CH:5]=[CH:4][N:3]=1.[F:17][C:18]1[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][C:21]([NH2:22])=[C:20]([O:28][CH3:29])[CH:19]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CC(O)CCC>C(Cl)Cl>[F:17][C:18]1[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][C:21]([NH:22][C:2]2[N:7]=[C:6]([C:8]3[CH:9]=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)=[C:20]([O:28][CH3:29])[CH:19]=1

Participants

6

Reactant 4

HCID 223862-PentanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 574290724-Fluoro-2-methoxy-5-nitroaniline2×HCID 717430803-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridine2×

Product 1

HCID 71240784N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amineYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (Intermediate 152, 1.476 g, 6.40 mmol), 4-fluoro-2-methoxy-5-nitroaniline (Intermediate 23, 1.310 g, 7.04 mmol), p-toluenesulfonic acid monohydrate (1.339 g, 7.04 mmol) and 2-pentanol (45 mL) was heated at 125° C. for 22 h. After cooling, the mixture was filtered. The solid was washed with CH3OH, diethyl ether and then dried on the filter to give a brown solid. The solid was dissolved in CH2Cl2 and this solution was washed with sat. NaHCO3 (×3), water and brine, then dried (MgSO4) and concentrated in vacuo. The resulting residue was triturated in boiling CH3CN and then allowed to cool. The resulting solid was collected by filtration and air dried to give the title compound (1.29 g, 53%) as a brown solid; 1H NMR: 4.03 (3H, s), 7.11 (1H, td), 7.37 (1H, d), 7.41 (1H, d), 7.43-7.48 (1H, m), 8.45 (1H, d), 8.51 (1H, s), 8.58 (1H, d), 8.82-8.84 (2H, m), 9.00 (1H, d); m/z: ES+ MH+ 381.54.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. washThe solid was washed with CH3OH, diethyl ether
  4. customdried on the
  5. filtrationfilter
  6. customto give a brown solid
  7. washthis solution was washed with sat. NaHCO3 (×3), water and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was triturated
  11. temperatureto cool
  12. filtrationThe resulting solid was collected by filtration and air
  13. customdried

Sources & evidence

ORD record
ord-23c82863d348400389e54d47160d4bc1
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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