Hydrogen Bromide → 9-Bromo camptothecin

HRID 341845

Reaction equation

HRID 341845 reaction equation
N([O-])=O.[Na+].[CH3:5][CH2:6][C@@:7]1([OH:31])[C:12](=[O:13])[O:11][CH2:10][C:9]2[C:14]([N:16]3[C:28](=[CH:29][C:8]1=2)[C:27]1[N:26]=[C:25]2[C:20]([C:21](N)=[CH:22][CH:23]=[CH:24]2)=[CH:19][C:18]=1[CH2:17]3)=[O:15].[BrH:32]>O>[CH3:5][CH2:6][C@@:7]1([OH:31])[C:12](=[O:13])[O:11][CH2:10][C:9]2[C:14]([N:16]3[C:28](=[CH:29][C:8]1=2)[C:27]1[N:26]=[C:25]2[C:20](=[CH:19][C:18]=1[CH2:17]3)[C:21]([Br:32])=[CH:22][CH:23]=[CH:24]2)=[O:15]

Participants

5

Reactant 3

HCID 260Hydrogen Bromide2×HCID 724029-AminocamptothecinHCID 23668193Sodium Nitrite

Product 1

HCID 102960989-Bromo camptothecin

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

2.15 g of NaNO2 in 40 mL of H2O were dropped at 5° C. into a solution of 9 g of 9-amino-camptothecin in 850 mL of 16% HBr. After 1 hr at r.t. the solution was dropped in a flask containing 19 g of CuBr in 200 mL of 16% HBr at 70° C. The reaction was allowed to stay at 70° C. for 2 hr, then it was poured in cold water. The precipitate was filtered and the mother liquors were extracted with CH2Cl2 ; the organic extract dried and evaporated was combined with the precipitate and purified by flash chromatography (eluent: CH2Cl2 /CH3OH=95/5) to give 8.19 g of the title product. (HPLC assay: 97.3%) 1H-NMR 400 MHz (DMSO-d6): d=8.87 (s, 1H), 8.20 (d, J=8.5, 1H), 8.06 (d, J=7.32, 1H), 7.81-7.75 (m, 1H), 7.35 (s, 1H), 6.53 (s, 1H), 5.42 (s, 2H), 5.32 (s, 2H), 1.89-1.82 (m, 2H), 0.87 (t, J=7.32, 3H). MS (FD): M+ =427.

Workup

  1. additionAfter 1 hr at r.t. the solution was dropped in a flask
  2. filtrationThe precipitate was filtered
  3. extractionthe mother liquors were extracted with CH2Cl2
  4. extractionthe organic extract
  5. customdried
  6. customevaporated
  7. custompurified by flash chromatography (eluent: CH2Cl2 /CH3OH=95/5)

Sources & evidence

ORD record
ord-083ee0dffdbc48b493d9bcc48e2bf997
Source dataset
uspto-grants-1999_01
Patent number
US05856333

Linked notes

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