p-Toluenesulfonic acid → Cositecan
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:27][CH2:28][C@@:29]1([OH:58])[C:34](=[O:35])[O:33][CH2:32][C:31]2[C:36]([N:38]3[C:50](=[CH:51][C:30]1=2)[C:49]1N=C2C(C(CC[Si](C)(C)C)=CC=C2)=C[C:40]=1[CH2:39]3)=[O:37]>C(O)(=O)C.C1(C)C=CC=CC=1>[CH3:27][CH2:28][C@@:29]1([OH:58])[C:34](=[O:35])[O:33][CH2:32][C:31]2[C:36]([N:38]3[C:50](=[CH:51][C:30]1=2)[C:49]1[C:40](=[C:8]([CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[C:3]2[C:2]([N:1]=1)=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH2:39]3)=[O:37]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 100 °C
Procedure
To a solution of 1-(2-amino-phenyl)-3-trimethylsilanyl-propan-1-one (3) (34 mg) and CDE ring moiety (4) (24 mg) in acetic acid (0.5 mL) and toluene (1 mL) was added p-toluenesulfonic acid (1 mg). The reaction solution was stirred for 20 hours at 100° C. After cooling to room temperature, the reaction solution was concentrated under reduced pressure and the residue was washed with hexane (10 mL), water (10 mL), and a mixture of acetone (5 mL) and hexane (5 mL). The yellow solid was evaporated to dryness in vacuo to yield 39 mg (98% Yield) of BNP1350 (Karenitecin; Cositecan; 7-(2′-trimethylsilyl)ethyl camptothecin; IUPAC Nomenclature: (4S)-4-ethyl-4-hydroxy-11-[2-(trimethylsilyl)ethyl]-1H-pyrano[3′:4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione).
Workup
- temperatureAfter cooling to room temperature
- concentrationthe reaction solution was concentrated under reduced pressure
- washthe residue was washed with hexane (10 mL), water (10 mL)
- additiona mixture of acetone (5 mL) and hexane (5 mL)
- customThe yellow solid was evaporated to dryness in vacuo
Sources & evidence
- ORD record
- ord-5bce4e5af9ea4870a0247770e7197424
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08722886B1
Reaction notes
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