1,3,5-Triazine → Rizatriptan

HRID 507382

Reaction equation

HRID 507382 reaction equation
C1(N)C(F)=C(F)C(F)=[C:3]([NH2:10])C=1F.Cl.Cl.Cl.Cl.[CH3:17][N:18]([CH3:35])[CH2:19][CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([CH2:30][NH:31][NH:32][CH:33]=O)[CH:28]=2)[NH:23][CH:22]=1.N1C=NC=NC=1>C(O)C>[CH3:17][N:18]([CH3:35])[CH2:19][CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([CH2:30][N:31]3[CH:3]=[N:10][CH:33]=[N:32]3)[CH:28]=2)[NH:23][CH:22]=1

Participants

5

Reactant 3

HCID 92621,3,5-TriazineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 131728313Formic acid N'-[3-(2-dimethylamino-ethyl)-1H-indol-5-ylmethyl]-hydrazide, dihydrochloride

Product 1

HCID 5078RizatriptanYield 84%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of the dihydrochloride of formic acid N′-[3-(2-dimethylamino-ethyl)-1H-indol-5-ylmethyl]-hydrazide (Example 18; 6.665 g, 20 mmol), and 1,3,5-triazine (1.081 g, 13.3 mmol) in ethanol (50 ml) is heated at reflux for six hours under a nitrogen atmosphere. From the slightly hazy yellow solution, the solvent is removed on the rotavapor, and the yellow residue is stirred with sodium hydroxide (100 ml 2N solution) and chloroform (100 ml). The organic layer is separated, washed with water (100 ml) and brine (100 ml) and dried (sodium sulfate). Removal of the solvent gives the product (4.54 g, 84%) as a slightly brown oil which solidifies on standing. 1H-NMR (CDCl3, 300 MHz) δ 2.26 (s, 6H, N(CH3)2); 2.56 (m, 2H, CH2); 2.83 (m, 2H, CH2NMe2); 5.27 (s, 2H, CH2N); 6.88 (d, 1H, J=2.0 Hz, H-2); 6.92 (dd, 1H, J=8.2 Hz, J=1.8 Hz, H-6); 7.15 (d, 1H, H-7); 7.40 (d, 1H, H-4); 7.84 (s, 1 H, triazol H-?); 7.89 (s, 1H, triazol H-?); 9.24 (br s, 1H, NH). 13C-NMR (CDCl3, 75 MHz) δ 23.68 (CH2); 45.50 (N(CH3)2); 54.88 (CH2N); 60.31 (CH2NMe2); 112.18 (C-7); 114.01 (C-3); 119.26 (C-4); 122.26 (C-6); 123.24 (C-2); 124.94 (C-5); 127.87 (C-9); 136.53 (C-8); 143.00 (triazol C-5); 151.88 (triazol C-3).

Workup

  1. temperatureat reflux for six hours under a nitrogen atmosphere
  2. customFrom the slightly hazy yellow solution, the solvent is removed on the rotavapor
  3. customThe organic layer is separated
  4. washwashed with water (100 ml) and brine (100 ml)
  5. dry with materialdried (sodium sulfate)
  6. customRemoval of the solvent

Sources & evidence

ORD record
ord-bf7c0f2c1b9644caa0322a77fa1ee6d5
Source dataset
uspto-grants-2010_08
Patent number
US07786156B2

Linked notes

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