Trifluoroacetic acid → N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrido[3,4-d]-pyrimidine-4,6-diamine

HRID 511795Notes

Reaction equation

HRID 511795 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25]([NH:27]CC4C=CC(OC)=CC=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25]([NH2:27])[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 7519AnisoleHCID 86668931N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

Product 1

HCID 86668932N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrido[3,4-d]-pyrimidine-4,6-diamineYield 89%

Procedure

To a stirred heterogeneous mixture of compound 212 (2.88 g, 5.77 mmol) and DCVI (60 ml) was added trifluoroacetic acid (4.38 ml, 57.7 mmol), followed by anisole (1.27 ml, 11.5 mmol), and the mixture was stirred further at room temperature. After 72 h another batch of trifluoroacetic acid (4.38 ml, 57.7 mmol) was added and stirred further for 49 h. It was poured into petroleum ether (250 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 (250 ml). The solid left behind was dissolved in acetone (150 mL) and 5M NH3 (125 ml) added at 0° C. The mixture was stirred at room temperature for 30 min. The solid was collected and washed successively with acetone/water (1:4) (5×30 ml), petroleum ether/ethyl acetate=3:1 (5×30 ml), and dried to give N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrido[3,4-d]-pyrimidine-4,6-diamine (221) (1.94 g, 89%), mp 247-250° C.; 1H NMR. δ [(CD3)2SO] 9.64 (s, 1H), 8.68 (s, 1H), 8.62-8.56 (m, 1H), 8.33 (s, 1H), 8.06 (d, J=2.6 Hz, 1H), 7.88 (td, J=7.7, 1.8 Hz, 1H), 7.73 (dd, J=9.0, 2.6 Hz, 1H), 7.58 (br d, J=7.8 Hz, 1H), 7.40-7.34 (m, 1H), 7.26 (d, J=9.0 Hz, 1H), 7.12 (s, 1H), 6.23 (s, 2H), 5.29 (s, 2H). Anal. Calcd for C19H13ClN6O.1.5H2O: C, 56.23; H, 4.47; N, 20.71%. Found C, 56.55; H, 4.45; N, 20.42%.

Workup

  1. stirringstirred further for 49 h
  2. stirringstirred at room temperature for ca. 20 min
  3. customPetroleum ether layer was decanted
  4. waitThe solid left behind
  5. dissolutionwas dissolved in acetone (150 mL)
  6. addition5M NH3 (125 ml) added at 0° C
  7. stirringThe mixture was stirred at room temperature for 30 min
  8. customThe solid was collected
  9. washwashed successively with acetone/water (1:4) (5×30 ml), petroleum ether/ethyl acetate=3:1 (5×30 ml)
  10. customdried

Sources & evidence

ORD record
ord-224f5b43f5474a10a49cc85f30f2556e
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Reaction notes

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