Trifluoroacetic acid → N4-(3,4-dichlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine

HRID 511800Notes

Reaction equation

HRID 511800 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH:20]CC4C=CC(OC)=CC=4)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH2:20])[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86668934N4-(3,4-dichlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

Product 1

HCID 86668935N4-(3,4-dichlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamineYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred heterogeneous mixture of compound 213 (2.50 g, 5.86 mmol) and DCM (60 ml) was added trifluoroacetic acid (4.49 ml, 58.6 mmol), followed by anisole (1.28 mL, 11.7 mmol), and the mixture was stirred further at room temperature for 43 h. It was poured into petroleum ether (600 mL) and stirred at room temperature for ca. 20 min. Petroleum ether layer was decanted and discarded. The process was repeated with more petroleum ether (300 mL). To the solid left behind was added 5M NH3 (80 mL) at 0° C. and stirred at room temperature for 15 min. The solid was collected and washed successively with water (6×10 mL), petroleum ether-ethyl acetate=3:1 (3×20 mL), and dried to give N4-(3,4-dichlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine (222) (1.76 g, 98%), mp 277-280° C.; 1H NMR δ [(CD3)2SO] 9.83 (s, 1H), 8.73 (s, 1H), 8.42 (s, 1H), 8.34 (d, J=2.5 Hz, 1H), 7.92 (dd, J=8.8, 2.5 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.14 (s, 1H), 6.30 (s, 2H). Anal. Calcd for C13H9Cl2N5.0.5H2O: C, 49.54; H, 3.20; N, 22.22. Found C, 49.70; H, 3.08; N, 22.28.

Workup

  1. stirringstirred at room temperature for ca. 20 min
  2. customPetroleum ether layer was decanted
  3. waitTo the solid left behind
  4. additionwas added 5M NH3 (80 mL) at 0° C.
  5. stirringstirred at room temperature for 15 min
  6. customThe solid was collected
  7. washwashed successively with water (6×10 mL), petroleum ether-ethyl acetate=3:1 (3×20 mL)
  8. customdried

Sources & evidence

ORD record
ord-8b2c87909806431b8af58f7f219b0bf0
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Reaction notes

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