Dimethylformamide → (2S)-2,6-bis((((tert-butoxy)carbonyl)amino))hexanoic acid

HRID 1645416Notes

Reaction equation

HRID 1645416 reaction equation
C(OC(NN([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H](C(O)=O)CCCCN)=O)(C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2[CH2:59][CH2:58][CH2:57][CH2:56]2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[OH:60][C:61]1[C:69]2N=NNC=2C=C[CH:62]=1.[CH3:70]N1CCOCC1.[OH:77][C:78](CCCC[C@H]1[C@@H]2[C@@H](NC(N2)=O)CS1)=[O:79].C[N:94]([CH3:97])[CH:95]=[O:96]>>[CH3:26][C:23]([O:22][C:20]([NH:19][CH2:59][CH2:58][CH2:57][CH2:56][C@H:97]([NH:94][C:95]([O:60][C:61]([CH3:69])([CH3:70])[CH3:62])=[O:96])[C:78]([OH:79])=[O:77])=[O:21])([CH3:24])[CH3:25]

Participants

7

Reactant 6

HCID 6228Dimethylformamide2×HCID 79724-Methylmorpholine2×HCID 171548BiotinHCID 2724699PyBOP2×HCID 87143421Di(t-butoxycarbonylamino)-l-lysineHCID 178418300HCID 178418300, compound2×

Product 1

HCID 7349648(2S)-2,6-bis((((tert-butoxy)carbonyl)amino))hexanoic acid

Procedure

Di-(t-Butoxycarbonylamino)-L-lysine (0.11 g, 20 μmole), benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) (0.10 g, 20 μmole), Hydroxybenzotriazole (HOBt) (0.03 g, 20 μmole) and N-methylmorpholine (NMM) (0.04 mL, 40 μmole) were dissolved in 1 mL dimethylformamide (DMF) and stirred for 1 minute. Then the mixture was contacted with beads to which the amino linker oligonucleotides (1 μmole) prepared in Example 1 were bound, and stirred for 1 hour. After being washed with dimethylformamide and dichloromethane, each three times, the bead was placed in 25% TFA/CH2Cl2 and stirred for 30 minutes. The bead was washed with dimethylformamide and dichloromethane, each three times. Biotin (0.05 g, 20 μmole), benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) (0.10 g, 20 μmole), Hydroxybenzotriazole (HOBt) (0.03 g, 20 μmole) and NMM (0.04 mL, 40 μmole) were dissolved in 1 mL dimethylformamide (DMF) and were stirred for 1 minute. Then, the mixture was contacted with beads to which the amino linker oligonucleotides (1 μmole) were bound. The beads were stirred for 1 hour, and washed with dimethylformamide and dichloromethane, each three times. To the beads, 2 mL of saturated NH4OH was added and placed at 60° C. for 8 hours. The solid part was isolated out from the centrifuge, and the liquid part was collected and dried under vacuum. The obtained biotin-labeled oligonucleotides were purified by RP-HPLC and freeze-dried, to produce the pure entitle compound in solid phase.

Workup

  1. stirringstirred for 1 hour
  2. washAfter being washed with dimethylformamide and dichloromethane
  3. stirringstirred for 30 minutes
  4. washThe bead was washed with dimethylformamide and dichloromethane
  5. stirringwere stirred for 1 minute
  6. stirringThe beads were stirred for 1 hour
  7. washwashed with dimethylformamide and dichloromethane
  8. additionTo the beads, 2 mL of saturated NH4OH was added
  9. waitplaced at 60° C. for 8 hours
  10. customThe solid part was isolated out from the centrifuge
  11. customthe liquid part was collected
  12. customdried under vacuum
  13. customwere purified by RP-HPLC
  14. customfreeze-dried
  15. customto produce the

Sources & evidence

ORD record
ord-280910bf23ef48b09b3b83d32a7b3b47
Source dataset
uspto-grants-2012_02
Patent number
US08124756B2

Reaction notes

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