1-Chloro-4-(chloromethyl)benzene → HCID 11224374, compound

HRID 1172569Notes

Reaction equation

HRID 1172569 reaction equation
[CH:1]12[CH2:8][N:7]([C:9](OC(C)(C)C)=O)[CH2:6][CH:5]1[CH2:4][CH2:3][NH:2]2.[O:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[C:21]1[N:34]=[C:24]2[N:25]=[C:26](S(C)(=O)=O)[N:27]=[C:28]([NH2:29])[N:23]2[N:22]=1.CCN(CC)CC.[Cl:42][C:43]1[CH:50]=[CH:49][C:46](CCl)=[CH:45][CH:44]=1>CC#N>[Cl:42][C:43]1[CH:50]=[CH:49][C:46]([CH2:9][N:7]2[CH2:6][CH:5]3[CH:1]([N:2]([C:26]4[N:27]=[C:28]([NH2:29])[N:23]5[N:22]=[C:21]([C:17]6[O:16][CH:20]=[CH:19][CH:18]=6)[N:34]=[C:24]5[N:25]=4)[CH2:3][CH2:4]3)[CH2:8]2)=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 8471Triethylamine2×HCID 99708822-(Furan-2-yl)-5-(methylsulfonyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amineHCID 225622051,1-Dimethylethyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate

Product 1

HCID 11224374HCID 11224374, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Tert-butyl 2,7-diazabicyclo[3.3.0]octane-7-carboxylate (0.5 mmol; see U.S. Pat. No. 5,071,999) was added to a mixture of 2-furan-2-yl-5-methanesulfonyl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (0.5 mmol, 1 eq.; see J. Chem. Soc. Perkin Trans. 1, 801 (1995)) and Et3N (0.6 mmol) in 5 mL of CH3CN. The reaction mixture was stirred at reflux for 2 hours. It was then cooled to room temperature and concentrated. The resulting residue was taken up in EtOAc, washed with brine, dried with Na2SO4, and concentrated under reduced pressure. This material (1-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid tert-butyl ester) was dissolved in 2 mL of 25% TFA in CH2Cl2 and allowed to stand at room temperature for 2 hours. It was then concentrated and the resulting residue was dissolved in 3 mL of CH3CN along with 0.5 mmol of 4-chlorobenzyl chloride and 0.8 mmol of Et3N. The resulting reaction mixture was stirred at room temperature for 18 hours. It was then concentrated and purified by preparative HPLC to afford the title compound. 1H NMR (400 Hz, DMSO-d6) δ 8.20 (brs, 1H), 7.70 (d, J=1.0 Hz, 1H), 7.10 (d, J=3.6 Hz, 1H), 7.0-7.30 (m, 4H) 6.60 (dd, J=3.6, 1.0 Hz, 1H), 4.80 (brs, 2H), 2.30-3.8 (m, 10H). MS m/z: 438 [M+H]+.

Workup

  1. temperatureat reflux for 2 hours
  2. concentrationconcentrated
  3. washwashed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThis material (1-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid tert-butyl ester) was dissolved in 2 mL of 25% TFA in CH2Cl2
  7. concentrationIt was then concentrated
  8. customThe resulting reaction mixture
  9. stirringwas stirred at room temperature for 18 hours
  10. concentrationIt was then concentrated
  11. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-5c99a317bf3145dab1b81a6c6abe5ad5
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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