Pyridine → HCID 46929363, compound

HRID 1753946Notes

Reaction equation

HRID 1753946 reaction equation
[CH2:1]([N:3]([CH2:23][CH3:24])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([F:19])[CH:16]=3)[N:11]([CH2:20][CH2:21][OH:22])[C:10]=2[CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].N1C=CC=CC=1.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>ClCCl>[CH2:23]([N:3]([CH2:1][CH3:2])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([F:19])[CH:16]=3)[N:11]([CH2:20][CH2:21][O:22][S:32]([CH3:31])(=[O:34])=[O:33])[C:10]=2[CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:24]

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 66679067HCID 66679067, compound

Product 1

HCID 46929363HCID 46929363, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-fluoro-9-(2-hydroxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (37) (460 mg, 1.4 mmol) in dichloromethane (20 mL) was added pyridine (1.11 g, 14.0 mmol, 1.1 mL). The reaction was cooled to 0° C. and methanesulfonyl chloride (722 mg, 6.3 mmol, 0.5 mL) was added. The reaction was allowed to warm to room temperature overnight. The mixture was washed with 2 N HCl (2×30 mL) and water (2×30 mL), dried and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with petrol (A) and ethyl acetate (B) (0-100% (B), 10 g, 45 CV, 30 mL/min) then triturated with diethyl ether to afford 166 mg (30%) of methanesulfonic acid 2-(4-diethylcarbamoyl-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester as a white solid. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 12.9, 15.0, 21.1, 27.7, 36.1, 36.7, 40.6, 41.7, 67.8, 103.3 (d, JCF=23 Hz), 108.7, 109.0, 109.1, 109.4 (d, JCF=5 Hz), 126.9 (d, JCF=10 Hz), 132.4, 138.4, 156.1, 159.2, and 173.3.

Workup

  1. temperatureto warm to room temperature overnight
  2. washThe mixture was washed with 2 N HCl (2×30 mL) and water (2×30 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by silica gel chromatography
  6. washeluting with petrol (A) and ethyl acetate (B) (0-100% (B), 10 g, 45 CV, 30 mL/min)
  7. customthen triturated with diethyl ether

Sources & evidence

ORD record
ord-be2404258f9843f78b99dcd0d11901f8
Source dataset
uspto-grants-2015_10
Patent number
US09168317B2

Reaction notes

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