Water → HCID 68283612, compound

HRID 1630574Notes

Reaction equation

HRID 1630574 reaction equation
CS(O[CH:6]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH2:7][N:8]1[C:16]2[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[C:10]2[CH2:18][N:19]([CH3:22])[CH2:20][CH2:21][C:9]1=2)(=O)=O.O.[CH3:31][NH2:32]>>[CH3:22][N:19]1[CH2:20][CH2:21][C:9]2[N:8]([CH2:7][CH:6]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[NH:32][CH3:31])[C:16]3[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[C:10]=2[CH2:18]1

Participants

4

Reactant 3

HCID 962WaterHCID 6329MethylamineHCID 86677146HCID 86677146, compound

Product 1

HCID 68283612HCID 68283612, compound

Procedure

2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(4-fluorophenyl)ethyl methane sulfonate (250 mg, 0.6 mmol) in methyl amine (40% solution in water, 5 mL) was heated at 100° C. for 4 h. The progress of the reaction was monitored by TLC and LCMS. 10 mL of water was added to the reaction mixture and then extracted with EtOAc (2×50 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to obtain the crude product, which was purified by reverse phase HPLC to obtain 2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(4-fluorophenyl)-N-methyl ethanamine (30 mg) as the TFA salt. 1H NMR (CDCl3, freebase): δ (ppm): 7.32 (t, 2H), 7.24 (m, 1H), 7.21 (s, 1H), 7.01 (m, 3H), 3.91 (m, 2H), 3.65 (dd, 2H), 2.80 (m, 3H), 2.62 (m, 1H), 2.54 (s, 3H), 2.45 (s, 3H), 2.14 (s, 3H). Chiral HPLC separated the racemate into enantiomers II-12a-b.

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customto obtain the crude product, which
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-0bef4ec98020491e88290ef7c1596c4a
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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