Dicyclohexylcarbodiimide → Deacetylvinblastine 3-aminopropylamide norleucine amide

HRID 366412Notes

Reaction equation

HRID 366412 reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:7]([OH:9])=O)[CH2:3][CH2:4][CH2:5][CH3:6].C1C=CC2N(O)N=[N:23]C=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH3:42][CH2:43][C@@:44]1([OH:97])[CH2:55][N:53]2[CH2:54][C@@H:46]([CH2:47][C@:48]([C:93]([O:95][CH3:96])=[O:94])([C:63]3[CH:68]=[C:67]4[C:69]56[C@@H:80]([N:81]([CH3:82])[C:66]4=[CH:65][C:64]=3[O:91][CH3:92])[C@@:79]([OH:87])([C:83]([O:85][CH3:86])=[O:84])[C@H:78]([OH:88])[C@:74]3([CH2:89][CH3:90])[CH:75]=[CH:76][CH2:77][N:72]([C@H:73]53)[CH2:71][CH2:70]6)[C:49]3[NH:62][C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[C:50]=3[CH2:51][CH2:52]2)[CH2:45]1.[NH2:98][CH2:99][CH2:100][CH2:101][NH-:102].C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:42][CH2:43][C@@:44]1([OH:97])[CH2:55][N:53]2[CH2:54][C@@H:46]([CH2:47][C@:48]([C:93]([O:95][CH3:96])=[O:94])([C:63]3[CH:68]=[C:67]4[C:69]56[C@@H:80]([N:81]([CH3:82])[C:66]4=[CH:65][C:64]=3[O:91][CH3:92])[C@@:79]([OH:87])([C:83]([O:85][CH3:86])=[O:84])[C@H:78]([OH:88])[C@:74]3([CH2:89][CH3:90])[CH:75]=[CH:76][CH2:77][N:72]([C@H:73]53)[CH2:71][CH2:70]6)[C:49]3[NH:62][C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[C:50]=3[CH2:51][CH2:52]2)[CH2:45]1.[NH2:98][CH2:99][CH2:100][CH2:101][NH-:102].[NH2:1][C@H:2]([C:7]([NH2:23])=[O:9])[CH2:3][CH2:4][CH2:5][CH3:6]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733747N-tert-Butoxycarbonyl-L-norleucineHCID 131721105Deacetylvinblastine 3-aminopropyl amide

Product 1

HCID 131722119Deacetylvinblastine 3-aminopropylamide norleucine amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a DMF solution (1 ml) of Boc-Nle (22 mg, 0.095 mmol) was added 318 μl of a 1M solution of HOBT (in NMP) followed by 280 μl of a 1M solution of DCC (in NMP). After 30 min., intermediate (11) (0.0624 mmol) was added in a 3.5 ml DMF. The pH of the reaction was adjusted ~7.5 with diisopropylethylamine. After stirring for 18 hrs the reaction was concentrated to an oil and the Boc protecting group removed by treating the oil with a 1:1 solution of TFA: CH2Cl2 (20 ml). After 5 min. the reaction was concentrated to dryness. Purification was achieved by preparative HPLC on a C-18 reverse phase support (Waters, Delta Pak). Buffer A=0.1% TFA-H2O; B=0.1% TFA-CH3CN. The crude product was loaded in 100% A buffer (100 ml) and a step gradient of 100% A to 30% A was used at a flow rate of 75 ml/min. Homogeneous product fractions were pooled and freeze-dried to yield (12).

Workup

  1. concentrationwas concentrated to an oil
  2. customthe Boc protecting group removed
  3. additionby treating the oil with a 1:1 solution of TFA
  4. concentrationAfter 5 min. the reaction was concentrated to dryness
  5. customPurification
  6. customfreeze-dried

Sources & evidence

ORD record
ord-a8ae13aa0ffd462082cbffd406d84937
Source dataset
uspto-grants-2000_10
Patent number
US06130204

Reaction notes

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