1,2-Dichloroethane → HCID 67235961, compound

HRID 1614856Notes

Reaction equation

HRID 1614856 reaction equation
[N:1](CCOCCOCC(=O)CCC(O)=O)=[N+:2]=[N-:3].C(Cl)CCl.[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]>ClCCl.CN(C1C=CN=CC=1)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].[N-:1]=[N+:2]=[N-:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 24360CamptothecinHCID 86676447HCID 86676447, compound

Product 1

HCID 67235961HCID 67235961, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 70 mg of 5-[2-(2-azidoethoxy)ethoxy]-4-oxopentanoic acid in 10 mL of dichloromethane was cooled in an ice-water bath, and treated with 55 mg of EDC, followed by 35 mg of DMAP and 50 mg of camptothecin. The reaction was then allowed to warm to room temperature and stirred overnight as the solution slowly became homogeneous. The reaction mixture was then concentrated and applied to a silica gel column, which was eluted first with 1-2% methanol in dichloromethane. The appropriate fractions were then concentrated to give the desired conjugate as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=0.98 (t, J=7.6H), 1.98 (quintet, J=7.2 Hz, 2H), 2.13-2.32 (complex m, 2H), 2.45 (t, J=7.6 Hz, 2H), 2.51-2.65 (complex m, 2H), 3.35 (t, J=5 Hz, 2H), 3.63-3.68 (m, 4H), 4.21-4.25 (m, 2H), 5.30 (br s, 2H), 5.41 (d, J=17.2 Hz, 1H), 5.68 (d, J=17.2 Hz, 1H), 7.21 (s, 1H), 7.68 (t, J=6.8 Hz, 1H), 7.84 (app t, J=8.4 Hz, 1H), 7.95 (d, J=8 Hz, 1H), 8.23 (d, J=8 Hz, 1H), 8.40 (s, 1H).

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. washwas eluted first with 1-2% methanol in dichloromethane
  3. concentrationThe appropriate fractions were then concentrated
  4. customto give the desired conjugate as a yellow solid

Sources & evidence

ORD record
ord-67b0568ff792482da12e6333cbc4e5b4
Source dataset
uspto-grants-2014_07
Patent number
US08765432B2

Reaction notes

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