Chlorosuccinimide → (13E)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[1-(3-phenyloxiran-2-yl)ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone

HRID 1840682Notes

Reaction equation

HRID 1840682 reaction equation
[CH3:1][C@H:2]1[C:20](=[O:21])[O:19][C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:16](=[O:17])[O:15][C@H:14]([C@@H:26](/[CH:28]=[CH:29]/[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH3:27])[CH2:13][CH:12]=[CH:11][C:9](=[O:10])[NH:8][C@H:7]([CH2:36][C:37]2[CH:38]=[CH:39][C:40]([O:44][CH3:45])=[C:41]([Cl:43])[CH:42]=2)[C:5](=[O:6])[NH:4][CH2:3]1.ClN1C(=[O:52])CCC1=O>COCCOC.O>[CH3:1][CH:2]1[C:20](=[O:21])[O:19][CH:18]([CH2:22][CH:23]([CH3:24])[CH3:25])[C:16](=[O:17])[O:15][CH:14]([CH:26]([CH:28]2[O:52][CH:29]2[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH3:27])[CH2:13][CH:12]=[CH:11][C:9](=[O:10])[NH:8][CH:7]([CH2:36][C:37]2[CH:38]=[CH:39][C:40]([O:44][CH3:45])=[C:41]([Cl:43])[CH:42]=2)[C:5](=[O:6])[NH:4][CH2:3]1

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 10077879Cryptophycin 3

Product 1

HCID 5468287(13E)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[1-(3-phenyloxiran-2-yl)ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

Likewise, cryptophycin 3 (about 40 mg, 0.063 mmol) is put into 2:1 DME/H2O (about 6 mL) and N-chlorosuccinimide (0.075 mmol) is added and is heated at about 60-70 C for about 24 hours. A further quantity of NCS (8 mg) is added and continue heating for about another 24 hours. The solvent is removed and the residue subject to HPLC (35% H2O/CH3CN 6 mL/min) to give the desired cryptophycin compounds. The resulting mixture is further purified by HPLC using methanol/water (about 4:1) to obtain the desired purified cryptophycin compounds.

Workup

  1. additionis added
  2. temperatureis heated at about 60-70 C for about 24 hours
  3. temperaturecontinue heating for about another 24 hours
  4. customThe solvent is removed

Sources & evidence

ORD record
ord-55a04787e78e46c88cf26bf63e930a3d
Source dataset
uspto-grants-2004_01
Patent number
US06680311B1

Reaction notes

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