Diisopropylethylamine → HCID 136389032, compound

HRID 1879452Notes

Reaction equation

HRID 1879452 reaction equation
C1C=CC(C(Cl)(C2C(Cl)=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(O[C:36]([NH:38][CH2:39][CH2:40][C:41]2[CH:42]=[CH:43][C:44]([OH:58])=[C:45]([N:47]=[N:48][C:49]3[CH:57]=[CH:56][C:52]([C:53]([OH:55])=[O:54])=[CH:51][CH:50]=3)[CH:46]=2)=[O:37])C2CC3C(=CC=CC=3)C=2C=CC=1.CCN(C(C)C)C(C)C.OC([CH2:71][CH2:72][CH2:73][CH2:74][C@H:75]1[C@@H:83]2[C@@H:78]([NH:79][C:80]([NH:82]2)=[O:81])[CH2:77][S:76]1)=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO.C(Cl)Cl>[C:36]([NH:38][CH2:39][CH2:40][C:41]1[CH:42]=[CH:43][C:44]([OH:58])=[C:45]([N:47]=[N:48][C:49]2[CH:50]=[CH:51][C:52]([C:53]([OH:55])=[O:54])=[CH:56][CH:57]=2)[CH:46]=1)(=[O:37])[CH2:71][CH2:72][CH2:73][CH2:74][C@H:75]1[C@@H:83]2[C@@H:78]([NH:79][C:80]([NH:82]2)=[O:81])[CH2:77][S:76]1

Participants

9

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 945242-Chlorotrityl chlorideHCID 171548BiotinHCID 2724699PyBOPHCID 136330138HCID 136330138, compound

Product 1

HCID 136389032HCID 136389032, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 2-chlorotrityl resin (186 mg, 0.26 mmol) was added DCM (2 ml), 4-[5-(N-fluorenyloxycarbonyl-2-Aminoethyl)-2-hydroxyphenylazo]-benzoic acid (130 mg, 0.26 mmol) and DIEA (175 μl, 1.0 mmol). The mixture was gently shaken overnight at room temperature. Dry methanol (0.2 ml) was added to cap any unreacted resin (10 min). The resin was dried, and the loading efficiency was determined to be 0.85 mmol/g. The resin was swelled with dry DMF (2 ml) for 30 minutes, drained and treated with a 20% solution of piperidine in DMF (2 ml) for 30 minutes. The resin was drained and washed with DMF (5×5 ml) to remove residual traced of piperidine. To the resulting resin was added dry DMF (2 ml), biotin (73.3 mg, 0.30 mmol), PYBOP (156.1 mg, 0.30 mmol) and DIEA (104.5 μl, 0.60 mmol), and the resin was gently shaken at room temperature overnight. The resulting resin was drained, washed with DMF (3×3 ml), DCM (3×3 ml) and hexanes (3×3 ml) and dried in vacuo. Cleavage of the resin was performed using a 10% solution of TFA in DCM (10×2 minutes each). The organic fractions were combined, concentrated in vacuo, and dried via azeotrope with toluene to afford the desired 4-[5-(N-biotinyl-2-Aminoethyl)-2-hydroxyphenylazo]-benzoic acid (2) as an orange solid (65 mg, 50% from the benzoic acid).

Workup

  1. customto cap any unreacted resin (10 min)
  2. customThe resin was dried
  3. waitThe resin was swelled with dry DMF (2 ml) for 30 minutes
  4. additiontreated with a 20% solution of piperidine in DMF (2 ml) for 30 minutes
  5. washwashed with DMF (5×5 ml)
  6. customto remove residual
  7. washwashed with DMF (3×3 ml), DCM (3×3 ml) and hexanes (3×3 ml)
  8. customdried in vacuo
  9. custom10×2 minutes
  10. concentrationconcentrated in vacuo
  11. dry with materialdried via azeotrope with toluene

Sources & evidence

ORD record
ord-f7c56909ba91433eaa15492c06d1cc1e
Source dataset
uspto-grants-2012_11
Patent number
US08314215B2

Reaction notes

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