Diisopropylamine → HCID 12088082, compound

HRID 986920Notes

Reaction equation

HRID 986920 reaction equation
FC1C=CC([C@@H](N)C)=CC=1.N1C(Cl)=NC(Cl)=NC=1Cl.[OH-].[NH4+].[Cl:22][C:23]1[N:28]=[C:27]([NH2:29])[N:26]=[C:25]([NH:30][C@H:31]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH3:32])[N:24]=1.[NH2:40][CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=1.C(NC(C)C)(C)C>C1COCC1>[Cl:22][C:23]1[N:28]=[C:27]([NH2:29])[N:26]=[C:25]([NH:30][C@H:31]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH3:32])[N:24]=1.[F:39][C:36]1[CH:37]=[CH:38][C:33]([C@@H:31]([NH:30][C:25]2[N:24]=[C:23]([NH:40][CH2:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=3)[N:28]=[C:27]([NH2:29])[N:26]=2)[CH3:32])=[CH:34][CH:35]=1

Participants

9

Reactant 6

HCID 7912DiisopropylamineHCID 7954Cyanuric chlorideHCID 14923Ammonium HydroxideHCID 759192-PyridineethanamineHCID 2779063(S)-1-(4-Fluorophenyl)-ethylamineHCID 12088081HCID 12088081, compound

Product 2

HCID 12088081HCID 12088081, compoundHCID 12088082HCID 12088082, compoundYield 144.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 4-Chloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]-1,3,5-triazine-2,6-diamine used was prepared from (1S)-1-(4-Fluorophenyl)ethylamine (resolved by the procedure of Takenaka, S. et al. J. Chem. Soc., Perkins Trans. 2 1978, 95-99), cyanuric chloride and ammonium hydroxide according to the procedure outlined in the first two steps of Scheme 3 and by the procedure as described in Examples 14 and 15. A stirred solution of 4-Chloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]-1,3,5-triazine-2,6-diamine (1.15 g, 4.30 mmol), 2-(2-aminoethyl)pyridine (0.58 g, 4.73 mmol), diisopropylamine (20 ml), and THF (10 ml) was heated at reflux for 18 hours and then concentrated under reduced pressure. The yellow residue was taken up in CH2Cl2 and washed with H2O and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on silica, eluting with 3% MeOH/CH2Cl2 to afford N2-[(1S)-1-(4-Fluorophenyl)ethyl]-N4-[2-(2-pyridinyl)ethyl]-1,3,5-triazine-2,4,6-triamine (free base) as a pale tan foam (1.10 g, 72%). 1H NMR (CDCl3) δ 8.51 (s, 1H), 7.56 (t, 1H), 7.31 (s, 2H), 7.08 (m, 1H), 6.97 (m, 3H), 5.88-5.44 (b m, 1H), 5.42-5.19 (b m, 1H), 5.15 (m, 1H), 4.95 (b s, 2H), 3.72 (d, 2H), 3.20-2.81 (b m, 2H), 1.47 (d, 3H). HPLC-MS (C-18, MeOH/H2O/TFA linear gradient elution, 5 ml/min, 220 nm): 1 peak at 0.84 minutes; MS (ES+) obs. m/z 353.83. A stirred solution of N2-[(1S)-1-(4-Fluorophenyl)ethyl]-N4-[2-(2-pyridinyl)ethyl]-1,3,5-triazine-2,4,6-triamine was treated with 10 mL of 1 N HCl in Et2O and allowed to stand at ambient temperature for 30 minutes. The mixture was concentrated by rotary evaporation to afford the titled compound as a pale white fine powder. LC/MS (C-18, MeOH/H2OTFA linear gradient elution, 5 ml/min, 220 nm): 1 peak at 0.86 minutes; MS (ES+) obsd m/z=354.26. MP=161° C.

Workup

  1. temperatureat reflux for 18 hours
  2. concentrationconcentrated under reduced pressure
  3. washwashed with H2O and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica
  8. washeluting with 3% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-e529beaca7e144e2a486e67c5cfbf6fd
Source dataset
uspto-grants-2003_10
Patent number
US06630469B2

Reaction notes

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