Dimethylformamide → HCID 67860518, compound

HRID 2081225Notes

Reaction equation

HRID 2081225 reaction equation
[F:1][C:2]1[C:10]2[NH:9][C:8]3[CH2:11][CH2:12][N:13]([CH2:16][C:17]4[N:18]=[CH:19][N:20](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[C:21]=4[CH3:22])[C:14](=[O:15])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:44][S:45](Cl)(=[O:47])=[O:46].[OH-:49].[Na+].CN([CH:54]=[O:55])C>O.C1COCC1.C(O)(=O)C>[C:54]([OH:55])(=[O:46])/[CH:6]=[CH:7]\[C:14]([OH:15])=[O:49].[F:1][C:2]1[C:10]2[N:9]([S:45]([CH3:44])(=[O:47])=[O:46])[C:8]3[CH2:11][CH2:12][N:13]([CH2:16][C:17]4[N:18]=[CH:19][NH:20][C:21]=4[CH3:22])[C:14](=[O:15])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24758Sodium hydride2×HCID 31297Methanesulfonyl chloride2×HCID 15712520HCID 15712520, compound

Product 1

HCID 67860518HCID 67860518, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 6-fluoro-2,3,4,5-tetrahydro-2-[[5-methyl-1-(triphenylmethyl) -1H-imidazol-4-yl]methyl]-1H-pyrido[4,3-b]indol-1-one (64 mg) in dry DMF (10 ml) was treated with sodium hydride (73% dispersion in oil; 6 mg), and stirred under nitrogen for 30 min. Methanesulphonyl chloride (10% v/v solution in DMF; 1 ml) was added dropwise and the mixture was stirred for a further 45 min at room temperature. Additional sodium hydride (6 mg) and methanesulphonyl chloride solution (2 ml) were then added, and stirring was continued for 2 h. The mixture was then added to water (75 ml) and extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with water (2×50 ml) and brine (2×50 ml), dried and concentrated in vacuo to give a gum. This was dissolved in water (5 ml), glacial acetic acid (5 ml) and THF (5 ml), and heated to reflux for 2 h. The reaction mixture was then added to 2N sodium hydroxide (50 ml) and extracted with ethyl acetate (2×50 ml). The combined, dried organic extracts were adsorbed onto silica and purified by FCC eluting with System A (100:8:1) to give the free base of the title compound (24 mg). This was triturated with ether, and then dissolved in hot methanol (2 ml). Maleic acid (7.4 mg) was added, and the resulting solution was heated and then concentrated in vacuo to give an oil. This was triturated with ether to give the title compound (20 mg), m.p. 205°-208°.

Workup

  1. stirringthe mixture was stirred for a further 45 min at room temperature
  2. stirringstirring
  3. waitwas continued for 2 h
  4. extractionextracted with ethyl acetate (3×50 ml)
  5. washThe combined organic extracts were washed with water (2×50 ml) and brine (2×50 ml)
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customto give a gum
  9. temperatureto reflux for 2 h
  10. extractionextracted with ethyl acetate (2×50 ml)
  11. custompurified by FCC
  12. washeluting with System A (100:8:1)

Sources & evidence

ORD record
ord-f382d6cc30814e48a4add914b70dfb5b
Source dataset
uspto-grants-1993_02
Patent number
US05183820

Reaction notes

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