1,2-Dichloroethane → HCID 178525997, compound

HRID 2174361Notes

Reaction equation

HRID 2174361 reaction equation
C1C=CC(C(Cl)(C2C(Cl)=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C2C(COC([NH:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][C:47]([OH:49])=[O:48])=O)C3C(=CC=CC=3)C=2C=CC=1.CCN(C(C)C)C(C)C.[NH:59]1[C:63]([CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][C:79]([OH:81])=O)=[N:62][N:61]=[N:60]1.ON1C(=O)C2C=CC=CC=2N=N1.C(Cl)CCl>ClCCl.CO>[NH:62]1[C:63]([CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][C:79]([NH:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][C:47]([OH:49])=[O:48])=[O:81])=[N:59][N:60]=[N:61]1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 81531DiisopropylethylamineHCID 945242-Chlorotrityl chlorideHCID 27560921-(9H-Fluoren-9-yl)-3-oxo-2,7,10-trioxa-4-azadodecan-12-oic acidHCID 178525417HCID 178525417, compound

Product 1

HCID 178525997HCID 178525997, compoundYield 38.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent4×

Procedure

To a suspension of 2-chlorotrityl chloride resin (2 g; crosslinked polystyrene) in dichloromethane were added a solution of (2-(2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy)ethoxy)acetic acid (0.55 g, 1.43 mmol) in dichloromethane (15 ml) and then a solution of DIPEA (0.65 ml) in dichloromethane (7 ml). After stirring at room temperature for 20 min methanol (2 ml) was added, and stirring was continued for 10 min. The resin was filtered, washed twice with dichloromethane and once with DMF. The resin was treated with a 20%-solution of piperidine in DMF (2×10 min), and washed extensively with DMF and dichloromethane. A solution of 16-(5-tetrazolyl)hexadecanoic acid (1.0 g, 3.08 mmol), 3-hydroxy-3,4-dihydro-1,2,3-benzotriazin-4-one (0.49 g, 3.0 mmol), and EDC (0.58 g, 3.03 mmol) in dichloromethane (25 ml) was added to the resin, and the mixture was shaken for 60 h. The resin was then extensively washed with DMF, dichloromethane and methanol, and suspended in a mixture of trifluoroacetic acid and dichloromethane (25:75; vol). After 0.5 h the resin was filtered, rinsed with dichloromethane, the combined filtrates were concentrated and the residue recrystallized from MeCN to yield 0.26 g of the title compound.

Workup

  1. additionwas added
  2. filtrationThe resin was filtered
  3. washwashed twice with dichloromethane and once with DMF
  4. additionThe resin was treated with a 20%-solution of piperidine in DMF (2×10 min)
  5. washwashed extensively with DMF and dichloromethane
  6. stirringthe mixture was shaken for 60 h
  7. washThe resin was then extensively washed with DMF, dichloromethane and methanol
  8. additionsuspended in a mixture of trifluoroacetic acid and dichloromethane (25:75; vol)
  9. filtrationAfter 0.5 h the resin was filtered
  10. washrinsed with dichloromethane
  11. concentrationthe combined filtrates were concentrated
  12. customthe residue recrystallized from MeCN

Sources & evidence

ORD record
ord-451d708f99e54933b37bce465f5c4ba9
Source dataset
uspto-grants-2015_06
Patent number
US09061067B2

Reaction notes

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