Pyridine → HCID 70293897, compound

HRID 1003289Notes

Reaction equation

HRID 1003289 reaction equation
N1C=CC=CC=1.[I:7]Cl.[CH3:9][CH2:10][C@@:11]1([OH:38])[C:16](=[O:17])[O:15][CH2:14][C:13]2[C:18]([N:20]3[C:24](=[CH:25][C:12]1=2)[C:23]1[N:26]=[C:27]2[C:32](=[CH:33][C:22]=1[CH2:21]3)[C:31]([CH2:34][CH:35]=[CH2:36])=[C:30]([OH:37])[CH:29]=[CH:28]2)=[O:19]>C(Cl)(Cl)Cl.[N+]([O-])([O-])=O.[Ag+]>[CH2:10]([C@:11]1([OH:38])[C:12]2[CH:25]=[C:24]3[N:20]([CH2:21][C:22]4[C:23]3=[N:26][C:27]3[C:32]([CH:33]=4)=[C:31]4[CH2:34][CH:35]([CH2:36][I:7])[O:37][C:30]4=[CH:29][CH:28]=3)[C:18](=[O:19])[C:13]=2[CH2:14][O:15][C:16]1=[O:17])[CH3:9]

Participants

6

Reactant 3

HCID 1049PyridineHCID 24640Iodine chlorideHCID 11603813ChiMMitecan

Product 1

HCID 70293897HCID 70293897, compound

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 6212ChloroformSolvent3×

Procedure

Silver nitrate (6.8 g, 0.040 mol) in dry, freshly distilled chloroform (50 mL) and dry pyridine (20 mL) was treated, dropwise, with stirring with a solution of iodine monochloride (6.48 g, 0.0400 mol) in dry chloroform (40 mL) over a two min period. After stirring for 15 min, the mixture was centrifuged; the supernatent was then added to a solution of (S)-9-allyl-10-hydroxycamptothecin (3.92 g, 0.00960 mol) in dry chloroform (15 mL) giving a deep amber solution which was stirred overnight at ambient temperature. The solution was concentrated to a small volume and then partitioned between methylene chloride and water. After separation of the layers, the aqueous phase was re-extracted with methylene chloride. The combined organic layer was washed successsively with ice cold 5% aq. HCl, dilute sodium thiosulfate solution, and finally with water. The solution was dried (sodium sulfate) and evaporated to a golden-brown residue which was triturated with a small amount of cold methanol to afford the title compound as a light brown solid. (2.25 g, 44%). 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J=4.3 Hz, 1H), 8.07 (d, J=9.2 Hz, 1H), 7.61 (s, 1H), 7.40 (dd, J=7.1 Hz and J=2.0 Hz, 1H), 5.73 (d, J=16.3 Hz, 1H), 5.29 (d, J=16.3 Hz, 1H), 5.26 (s, 2H), 5.20-5.10 (m, 1H), 3.83-3.81 (m, 1H), 3.72-3.70 (m, 1H), 3.57-3.54 (m, 1H), 3.49-3.46 (m, 1H), 3.39-3.38 (m, 1H), 1.92-1.84 (m, 2H), 1.03 (t, J=7.3 Hz, 3H). Anal.: (C23H19IN2O5.1/2H2O) calcd.: C, 51.22; H, 3.74; N, 5.19 found: C, 51.03; H, 3.56; N, 4.87.

Workup

  1. customgiving a deep amber solution which
  2. stirringwas stirred overnight at ambient temperature
  3. concentrationThe solution was concentrated to a small volume
  4. custompartitioned between methylene chloride and water
  5. customAfter separation of the layers
  6. extractionthe aqueous phase was re-extracted with methylene chloride
  7. washThe combined organic layer was washed successsively with ice cold 5% aq. HCl, dilute sodium thiosulfate solution
  8. dry with materialThe solution was dried (sodium sulfate)
  9. customevaporated to a golden-brown residue which
  10. customwas triturated with a small amount of cold methanol

Sources & evidence

ORD record
ord-36ece0a0b6484bb9867dee29038b740a
Source dataset
uspto-grants-2000_04
Patent number
US06046209

Reaction notes

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