Sodium Bicarbonate → Lurosetron

HRID 2081228Notes

Reaction equation

HRID 2081228 reaction equation
[F:1][C:2]1[C:10]2[N:9]([CH3:11])[C:8]3[CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl.O[CH2:31][C:32]1[N:33]=[CH:34][NH:35][C:36]=1[CH3:37].C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[F:1][C:2]1[C:10]2[N:9]([CH3:11])[C:8]3[CH2:12][CH2:13][N:14]([CH2:31][C:32]4[N:33]=[CH:34][NH:35][C:36]=4[CH3:37])[C:15](=[O:16])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 30847074-Methylimidazol-5-ylmethanolhydrochloride2×HCID 157125046-Fluoro-2,3,4,5-tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one

Product 1

HCID 172999LurosetronYield 128.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 6-fluoro-2,3,4,5-tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one (100 mg) in N-methylpyrrolidinone (10 ml) was treated with 4-toluenesulphonic acid monohydrate (17 mg) and 4-hydroxymethyl-5-methylimidazole hydrochloride (37 mg). The mixture was then heated to 125° for 18 h during which time three further portions of 4-hydroxymethyl-5-methylimidazole hydrochloride (37 mg) were added at 1,2 and 3 h respective. The solution was then poured into 8% sodium bicarbonate solution (100 ml) and extracted with dichloromethane (3×100 ml). The combined extracts were concentrated in vacuo and the N-methylpyrrolidinone was distilled at 100°. The residue was purified by FCC eluting with System A (200:8:1) to give the title compound (100 mg), t.l.c. (System A, 100:8:1) Rf 0.3.

Workup

  1. additionwere added at 1,2 and 3 h respective
  2. extractionextracted with dichloromethane (3×100 ml)
  3. concentrationThe combined extracts were concentrated in vacuo
  4. distillationthe N-methylpyrrolidinone was distilled at 100°
  5. customThe residue was purified by FCC
  6. washeluting with System A (200:8:1)

Sources & evidence

ORD record
ord-fc9e37b454ab473090598dc4a61664c5
Source dataset
uspto-grants-1993_02
Patent number
US05183820

Reaction notes

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