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

HRID 1842780Notes

Reaction equation

HRID 1842780 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.[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>[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[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)=[C:20]([O:28][CH3:29])[CH:19]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 574290724-Fluoro-2-methoxy-5-nitroaniline2×HCID 866773443-(2-Chloropyrimidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine2×

Product 1

HCID 71240760N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amineYield 37.5%

Reagents, catalysts & solvents 1

HCID 223862-PentanolSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-(2-chloropyrimidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (Intermediate 128, 3.6857 g, 15.70 mmol), 4-fluoro-2-methoxy-5-nitroaniline (Intermediate 23, 2.92 g, 15.70 mmol) and p-toluenesulfonic acid hydrate (3.29 g, 17.28 mmol) in 2-pentanol (100 mL) was stirred at 85° C. under an atmosphere of N2 for 1.5 h. The mixture was then concentrated in vacuo and the resulting reside was dissolved in CH2Cl2 (250 mL). This solution was washed with sat. NaHCO3 (2×100 mL), water (100 mL), and sat. brine (100 mL). The organic solution was concentrated in vacuo to give crude product. Purification by FCC, eluting with 0-10% CH3OH in CH2Cl2 provided an orange solid. This material was triturated with CH3OH to give a solid which was collected by filtration and dried in vacuo to give the title compound (2.26 g, 37%) as a yellow solid; 1H NMR: 1.75-1.86 (2H, m), 1.92-2.04 (2H, m), 3.09 (2H, t), 4.02 (3H, s), 4.12 (2H, t), 7.13 (1H, d), 7.35 (1H, d), 8.14 (1H, s), 8.25 (1H, s), 8.42 (1H, d), 9.02 (1H, d); m/z: ES+ MH+ 385.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. dissolutionthe resulting reside was dissolved in CH2Cl2 (250 mL)
  3. washThis solution was washed with sat. NaHCO3 (2×100 mL), water (100 mL), and sat. brine (100 mL)
  4. concentrationThe organic solution was concentrated in vacuo
  5. customto give crude product
  6. customPurification by FCC
  7. washeluting with 0-10% CH3OH in CH2Cl2
  8. customprovided an orange solid
  9. customThis material was triturated with CH3OH
  10. customto give a solid which
  11. filtrationwas collected by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-603d305fd23e49bea0991174bca978c6
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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