Diisopropylcarbodiimide → HCID 131729453, compound

HRID 1644016Notes

Reaction equation

HRID 1644016 reaction equation
CC(OC([NH:8][CH2:9][C:10]([OH:12])=[O:11])=O)(C)C.C(N=C=NC(C)C)(C)C.[CH3:22][CH2:23][C@@:24]1([OH:47])[C:29](=[O:30])[O:28][CH2:27][C:26]2[C:31]([N:33]3[C:45](=[CH:46][C:25]1=2)[C:44]1[N:43]=[C:42]2[C:37]([CH:38]=[CH:39][CH:40]=[CH:41]2)=[CH:36][C:35]=1[CH2:34]3)=[O:32]>C(Cl)Cl.CN(C)C1C=CN=CC=1.CS(C)=O>[CH3:22][CH2:23][C@@:24]1([OH:47])[C:29](=[O:30])[O:28][CH2:27][C:26]2[C:31]([N:33]3[C:45](=[CH:46][C:25]1=2)[C:44]1[N:43]=[C:42]2[C:37]([CH:38]=[CH:39][CH:40]=[CH:41]2)=[CH:36][C:35]=1[CH2:34]3)=[O:32].[NH2:8][CH2:9][C:10]([O-:12])=[O:11]

Participants

7

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 24360Camptothecin2×HCID 78288N-(tert-butoxycarbonyl)glycine

Product 1

HCID 131729453HCID 131729453, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

All chemicals, unless otherwise indicated, were purchased from Sigma Chemical Co. (St. Louis, Mo.) or Fisher Scientific (Houston, Tex.) and used as received. t-boc-glycine (0.31 g, 1.71 mmol; Bachem, Bioscience Inc., King of Prussia, Pa.) was dissolved in 20 mL of anhydrous methylene chloride at room temperature. To this solution was added 1,3-diisopropylcarbodiimide (DIPC, 267.7 mL, 1.71 mmol), 4-dimethylamino-pyridine (DMAP, 0.14 g, 1.14 mmol) and camptothecin (CPT, 0.20149 g, 0.57 mmol) at 0° C. While CPT (Sigma Chemical Co., St. Louis, Mo.) was dissolved in dimethyl sulfoxide (DMSO) because of its low solubility, the concentration of DMSO in working solutions was less than 1.0%; a concentration which did not have a significant effect on cells. The reaction mixture was allowed to warm to room temperature and incubated overnight. The product was washed with 0.1 N HCl, dried and evaporated under reduced pressure to yield the sold product. The product was recrystallized from methanol to give CPT-glycinate. The t-boc protection group was removed by dissolving the CPT-glycinate in a mixture of methylene chloride and trifluoracetic acid (TFA) (50:50) and stirring at room temperature for 3 hours. Solvent was evaporated under reduced pressure and precipitated using ether to give CPT-glycinate-TFA salt. CPT-glycinate-TFA salt (34.0 mg or 50 mg) and PEG-NHS (100 mg; MW ˜3400; Shearwater Corporation, Huntsville, Ala.) were added to methylene chloride (5 ml) and DIEA (50 ml) was added to adjust the pH to basic. The reaction was stirred for 3 hours at room temperature. The product was recrystallized from cold ether and dried under vacuum overnight.

Workup

  1. concentrationa concentration which
  2. washThe product was washed with 0.1 N HCl
  3. customdried
  4. customevaporated under reduced pressure
  5. customto yield the sold product
  6. customThe product was recrystallized from methanol

Sources & evidence

ORD record
ord-32d4a715569d48f8a3b0be2c8796c7ed
Source dataset
uspto-grants-2012_02
Patent number
US08124051B2

Reaction notes

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