Diisopropylcarbodiimide → Fmoc-Gly-Allyl

HRID 1749

Reaction equation

HRID 1749 reaction equation
[NH:1]([C:10]([O:12][CH2:13][CH:14]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]2[C:15]1=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11])[C@H:2]([C:7](O)=[O:8])CCCC.[CH3:27][C:28]1C=CC(C(N)C2C=CC=CC=2)=C[CH:29]=1.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.Cl.C1C=CC2N(O)N=NC=2C=1.CC(N=C=NC(C)C)C.N(C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)CC(O)=O>C(Cl)Cl.CN(C=O)C.CN(C=O)C.CN(C1C=CN=CC=1)C>[NH:1]([C:10]([O:12][CH2:13][CH:14]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]2[C:15]1=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11])[CH2:2][C:7]([CH2:29][CH:28]=[CH2:27])=[O:8]

Participants

9

Reactant 5

HCID 12734Diisopropylcarbodiimide3×HCID 757711-Hydroxybenzotriazole3×HCID 93124Fmoc-Gly-OHHCID 7009636(2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acidHCID 71310119MBHA resin

Product 1

HCID 131719722Fmoc-Gly-Allyl

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

0.848 g Fmoc-Nle (2.4 mmol) was coupled to 2.0 g MBHA resin (1.6 mmol) with 0.367 g HOBt (2.4 mmol) and 0.373 mL DIPCDI (2.4 mmol) in 20 mL DCM-DMF (1:1) for 2.3 h. The resin was washed 3 times with DMF, deprotected with 20 mL piperidine-DMF (1:1) for 30 min, and washed 3 times with DMF. 1.82 g allyl linker (3.2 mmol) was coupled to the resin with 0.489 g HOBt (3.2 mmol) and 0.497 mL DIPCDI (3.2 mmol) in 20 mL DMF for 18.5 h. The resin was washed 1 time with DMF and 2 times with DCM, deprotected twice with 20 mL TFA-DCM (9:1), first for 20 min, then for 10 min, washed 3 times with DCM, neutralized with 20 mL DIEA-DCM (1:9) for 15 min, and washed 1 time with DCM and 2 times with DMF. 1.43 g Fmoc-Gly (4.8 mmol) was esterified to the allyl resin with 0.735 g HOBt (4.8 mmol), 0.746 mL DIPCDI (4.8 mmol), and 0.059 g DMAP (0.48 mmol) in 20 mL DMF for 6.5 h. The resin was washed 1 time with DMF and 2 times with DCM and stored under vacuum overnight.

Workup

  1. washThe resin was washed 3 times with DMF
  2. washwashed 3 times with DMF
  3. washThe resin was washed 1 time with DMF and 2 times with DCM
  4. waitdeprotected twice with 20 mL TFA-DCM (9:1), first for 20 min
  5. waitfor 10 min
  6. washwashed 3 times with DCM
  7. waitneutralized with 20 mL DIEA-DCM (1:9) for 15 min
  8. washwashed 1 time with DCM and 2 times with DMF
  9. washThe resin was washed 1 time with DMF and 2 times with DCM
  10. customstored under vacuum overnight

Sources & evidence

ORD record
ord-c1ba761e373b418eb88a318c26b3d7f2
Source dataset
uspto-grants-1998_03
Patent number
US05726243

Linked notes

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