Piperazine → N~5~-{2-[4-(2,4-Difluorophenyl)piperazin-1-Yl]ethyl}-2-(Furan-2-Yl)[1,2,4]triazolo[1,5-A][1,3,5]triazine-5,7-Diamine

HRID 1181310Notes

Reaction equation

HRID 1181310 reaction equation
CO[CH:3](OC)[CH2:4][NH:5][C:6]1[N:11]=[C:10]([NH2:12])[N:9]2[N:13]=[C:14]([C:16]3[O:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[C:8]2[N:7]=1.C(O)(C(F)(F)F)=O.O.[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.N1CCNCC1.BrC1C=CC(F)=CC=1F.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.C(N(CC)CC)C>[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[N:39]1[CH2:40][CH2:41][N:42]([CH2:3][CH2:4][NH:5][C:6]2[N:11]=[C:10]([NH2:12])[N:9]3[N:13]=[C:14]([C:16]4[O:17][CH:18]=[CH:19][CH:20]=4)[N:15]=[C:8]3[N:7]=2)[CH2:43][CH2:44]1

Participants

9

Reactant 6

HCID 4837PiperazineHCID 676741-Bromo-2,4-difluorobenzeneHCID 27346371-(2,4-Difluorophenyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 22392675Trifluoroacetic acid waterHCID 69434374N5-(2,2-dimethoxy-ethyl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine

Product 1

HCID 44394716N~5~-{2-[4-(2,4-Difluorophenyl)piperazin-1-Yl]ethyl}-2-(Furan-2-Yl)[1,2,4]triazolo[1,5-A][1,3,5]triazine-5,7-Diamine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

The dimethyl acetal intermediate (40 mg, 0.13 mmol) from subpart (a) above was suspended in 2 mL of CH2Cl2 and 0.2 mL of 2:1 solution of TFA/H2O was added. The resulting reaction mixture was stirred at room temperature for 4 hours. It was then neutralized with 0.25 mL of triethylamine. 1-(2,4-Difluoro-phenyl)-piperazine (40 mg, 1.5 eq., prepared by reacting piperazine with 1-bromo-2,4-difluorobenzene according to the procedure described in WO 01/92264 A1), was added, followed by 140 mg of Na(OAc)3BH. The resulting reaction mixture was stirred at room temperature for 2 hours. It was then concentrated and then purified by preparative HPLC to afford N5-{2-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethyl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine. 1H NMR (DMSO-d6) δ 7.90 (br s, 2H), 7.80 (d, J=1.0 Hz, 1H), 7.05 (d, J=3.6 Hz, 1H), 7.10-7.50 (m, 3 H), 6.68 (dd, J=3.6 Hz, 1.0 Hz, 1H) 3.20-2.75 (m, 12 H) ppm. MS: m/z: 442 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. additionwas added
  3. customThe resulting reaction mixture
  4. stirringwas stirred at room temperature for 2 hours
  5. concentrationIt was then concentrated
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-676f22e3f4e945ae8cd1e29fe5a6d55f
Source dataset
uspto-grants-2007_10
Patent number
US07285550B2

Reaction notes

Loading…