Trifluoroacetic acid → 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyridin-2(1H)-one

HRID 632826Notes

Reaction equation

HRID 632826 reaction equation
COC1C=CC(C[O:8][C:9]2[C:14]([N:15]3[CH2:25][CH2:24][C:18]4[N:19]=[C:20]([NH2:23])[N:21]=[CH:22][C:17]=4[CH2:16]3)=[CH:13][CH:12]=[CH:11][N:10]=2)=CC=1.FC(F)(F)C(O)=O>ClCCl>[NH2:23][C:20]1[N:21]=[CH:22][C:17]2[CH2:16][N:15]([C:14]3[C:9](=[O:8])[NH:10][CH:11]=[CH:12][CH:13]=3)[CH2:25][CH2:24][C:18]=2[N:19]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 1212495836-{2-[(4-Methoxybenzyl)oxy]pyridin-3-yl}-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

Product 1

HCID 1212496083-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyridin-2(1H)-oneYield 40.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-{2-[(4-methoxybenzyl)oxy]pyridin-3-yl}-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine (1.77 g, 4.87 mmol) in dichloromethane (70 ml) was treated with trifluoroacetic acid (2.68 ml, 36.04 mmol) at room temperature. After stirring for 30 minutes, the solvent and excess acid was removed in vacuo and the residue was treated with ethyl acetate. Washing with sat'd NaHCO3(aq.) gave a yellow, amorphous precipitate. The solid was collected, washed with water, EtOAc, MeOH and dried (774 mg, 65%). The product was suspended in a 2:1 (v/v) mixture of water: MeOH (125 ml) and heated to boiling with vigorous stirring for 1.5 hours. The undissolved solid remaining was collected by filtration while the mixture was still hot and washed with water, MeOH, and dried to give the title compound (478 mg, 40%).

Workup

  1. customthe solvent and excess acid was removed in vacuo
  2. additionthe residue was treated with ethyl acetate
  3. washWashing with sat'd NaHCO3(aq.)
  4. customgave a yellow, amorphous precipitate
  5. customThe solid was collected
  6. washwashed with water, EtOAc, MeOH
  7. customdried (774 mg, 65%)
  8. additionThe product was suspended in a 2:1 (v/v) mixture of water
  9. temperatureMeOH (125 ml) and heated
  10. stirringwith vigorous stirring for 1.5 hours
  11. filtrationThe undissolved solid remaining was collected by filtration while the mixture
  12. washwashed with water, MeOH
  13. customdried

Sources & evidence

ORD record
ord-59281c67bd2e4884900ac7c2d78585f0
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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