5-fluoro-3-[(4-piperidinyl)methyl]-1H-indole → HCID 10113596, compound

HRID 1359050Notes

Reaction equation

HRID 1359050 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:26][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[CH:21][CH:20]=[CH:19]4)(=O)=O)=CC=1.[F:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[CH2:37][CH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>CS(C)=O>[F:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[CH2:37][CH:38]1[CH2:43][CH2:42][N:41]([CH2:12][CH:13]2[O:26][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[CH:21][CH:20]=[CH:19]4)[CH2:40][CH2:39]1

Participants

4

Reactant 2

HCID 112877165-fluoro-3-[(4-piperidinyl)methyl]-1H-indoleHCID 12042423HCID 12042423, compound

Product 1

HCID 10113596HCID 10113596, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
77.5 °C

Procedure

(2R)-2,3-Dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.46 g, 1.24 mmole) and 5-fluoro-3-(4-piperidinylmethyl)-1H-indole (1.00 g, 4.32 mmole) were combined in 40 mL of DMSO and heated at 75-80° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated sodium bicarbonate solution. The organic phase was removed, washed with saturated brine, dried over magnesium sulfate and concentrated to an oil in vacuum. This was column chromatographed on silica gel using first methylene chloride to elute impurities and then 3% methanol in methylene chloride to elute 0.200 g of the product as a yellow oil. The oil was crystallized from isopropanol with the addition of 0.040 g of oxalic acid to give 0.107 g of the (S)-enantiomer of the title compound as a light red solid (m.p. 184° C.), which contained both water and isopropanol.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between 400 mL each of ethyl acetate and saturated sodium bicarbonate solution
  3. customThe organic phase was removed
  4. washwashed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to an oil in vacuum
  7. customThis was column chromatographed on silica gel using first methylene chloride
  8. washto elute impurities
  9. wash3% methanol in methylene chloride to elute 0.200 g of the product as a yellow oil
  10. customThe oil was crystallized from isopropanol with the addition of 0.040 g of oxalic acid

Sources & evidence

ORD record
ord-4ca4083ace4d4ec0856f4ec6c202b13c
Source dataset
uspto-grants-2003_07
Patent number
US06599915B2

Reaction notes

Loading…