Piperidine → 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-(piperidin-1-yl)azetidin-1-yl)benzo[d]thiazole

HRID 2040964Notes

Reaction equation

HRID 2040964 reaction equation
[N+](C1C=CC(S(O[CH:14]2[CH2:17][N:16]([C:18]3[S:19][C:20]4[CH:26]=[C:25]([C:27]5[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=5)[CH:24]=[CH:23][C:21]=4[N:22]=3)[CH2:15]2)(=O)=O)=CC=1)([O-])=O.[NH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>CN(C)C=O>[CH3:32][N:30]1[CH:31]=[C:27]([C:25]2[CH:24]=[CH:23][C:21]3[N:22]=[C:18]([N:16]4[CH2:17][CH:14]([N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)[CH2:15]4)[S:19][C:20]=3[CH:26]=2)[CH:28]=[N:29]1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 866319061-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-yl 4-nitrobenzenesulfonate

Product 1

HCID 441240126-(1-methyl-1H-pyrazol-4-yl)-2-(3-(piperidin-1-yl)azetidin-1-yl)benzo[d]thiazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 1-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-yl 4-nitrobenzenesulfonate (Reference Example 3, 38 mg, 0.08 mmol), and piperidine (0.024 mL, 0.24 mmol) in N,N-dimethylformamide (0.5 mL) was heated at 160° C. under microwave irradiation for 15 minutes. The mixture was cooled to room temperature then purified by silica gel chromatography (60:30:10 hexane/dichloromethane/2 M NH3 in isopropanol). These product fractions were purified by silica gel chromatography again (79:20:1 to 70:25:5 hexane/dichloromethane/2 M NH3 in isopropanol). A final silica gel chromatographic purification was performed by first eluting the column with 100% dichloromethane to 80:20 dichloromethane/ethyl acetate followed by elution with 99:1 to 96:4 dichloromethane/methanol to provide 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-(piperidin-1-yl)azetidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.47-1.57 (m, 1H), 1.65 (pentet, J=5 Hz, 4H), 2.37-2.45 (m, 4H), 3.36-3.46 (m, 1H), 3.92 (s, 3H), 4.02-4.09 (m, 2H), 4.25 (t, J=8 Hz, 2H), 7.45 (d, J=8 Hz, 1H), 7.50 (dd, J=2, 8 Hz, 1H), 7.79 (s, 1H), 7.85 (d, J=2 Hz, 1H), 7.92 (s, 1H); MS (ESI) m/z 354 (M+H)+.

Workup

  1. customthen purified by silica gel chromatography (60:30:10 hexane/dichloromethane/2 M NH3 in isopropanol)
  2. customThese product fractions were purified by silica gel chromatography again (79:20:1 to 70:25:5 hexane/dichloromethane/2 M NH3 in isopropanol)
  3. customA final silica gel chromatographic purification
  4. washby first eluting the column with 100% dichloromethane to 80:20 dichloromethane/ethyl acetate
  5. washfollowed by elution with 99:1 to 96:4 dichloromethane/methanol

Sources & evidence

ORD record
ord-dc46c131133140eeb4638cca0da133e6
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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