Triethylamine → cis-3-Fluoro-1-{3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl}-4-[2-(trifluoromethyl)benzylamino]piperidine, oxalate salt

HRID 356682Notes

Reaction equation

HRID 356682 reaction equation
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3[CH2:15][CH2:16][CH2:17][OH:18])[CH:5]=1.CS(Cl)(=O)=[O:21].C(N(CC)CC)C.[F:31][C@H:32]1[C@@H:37]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[C:46]([F:49])([F:48])[F:47])[CH2:36][CH2:35][NH:34][CH2:33]1.[C:50](=[O:53])([O-:52])[O-].[K+].[K+]>O1CCCC1.CC(O)C>[C:17]([OH:18])(=[O:21])[C:50]([OH:52])=[O:53].[F:31][C@H:32]1[C@@H:37]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[C:46]([F:49])([F:47])[F:48])[CH2:36][CH2:35][N:34]([CH2:17][CH2:16][CH2:15][C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([N:4]4[CH:3]=[N:2][N:1]=[CH:5]4)[CH:7]=3)[NH:11][CH:10]=2)[CH2:33]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-olHCID 131720946cis-3-Fluoro-4-[2-(trifluoromethyl)benzylamino]piperidine

Product 1

HCID 131720945cis-3-Fluoro-1-{3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl}-4-[2-(trifluoromethyl)benzylamino]piperidine, oxalate saltYield 74.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Using a similar procedure to that described in Example 1, step 5, 3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol (0.2312 g, 0.954 mmol) was reacted with methanesulphonyl chloride (0.151 mL, 1.91 mmol) and triethylamine (0.266 mL, 1.91 mmol) in tetrahydrofuran (30 mL), followed by cis-3-fluoro-4-[2-(trifluoromethyl)benzylamino]piperidine (0.3950 g, 1.43 mmol) and potassium carbonate (0.2642 g, 1.91 mmol) in 2-propanol (30 mL). Purification by flash chromatography (alumina, CH2Cl2 --MeOH--NH3 (aq); 98:2:0.2; then silica gel, CH2Cl2 --MeOH--NH3 (aq); 94:6:0.6) gave 0.2096 g (44%) of the title compound, free base. The oxalate salt was prepared in MeOH--Et2O; mp 116°-120° C. Found: C, 52.70; H, 5.09; N, 12.22. Cl26 H28F4N6. 2C2H2O4 requires: C, 52.94; H, 4.74; N, 12.35%. δH (360 MHz, d6 -DMSO) 1.81 (1H, m), 1.92-2.03 (3H, m), 2.69-3.12 (7H, m), 3.30 (1H, m), 3.60 (1H, m), 3.99 (2H, s), 5.04 (1H, d, J=46.4 Hz), 7.31-7.33 (2H, m), 7.48-7.51 (2H, m), 7.66-7.71 (2H, m), 7.79 (1H, s), 7.84 (1H, d, J=7.4 Hz), 9.01 (2H, s), 11.17 (1H, s). m/e (ES+) 501 (M+H)+.

Workup

  1. customPurification by flash chromatography (alumina, CH2Cl2

Sources & evidence

ORD record
ord-987709715c14422a9fe67c266ad116ab
Source dataset
uspto-grants-1998_11
Patent number
US05837715

Reaction notes

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