1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Butyl 4-((3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinamido)methyl)-4-phenylpiperidine-1-carboxylate

HRID 1800829Notes

Reaction equation

HRID 1800829 reaction equation
[NH2:1][CH2:2][C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11]C(C)(C)C)=[O:10])[CH2:5][CH2:4]1.[F:22][C:23]1[C:24]([C:42]([OH:44])=O)=[N:25][CH:26]=[CH:27][C:28]=1[S:29][C:30]1[S:34][C:33]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=2)=[N:32][CH:31]=1.[CH3:45]CN=C=NCCCN(C)C.[CH:56]1[CH:57]=CC2N(O)N=N[C:60]=2[CH:61]=1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.O>[F:22][C:23]1[C:24]([C:42]([NH:1][CH2:2][C:3]2([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:4][CH2:5][N:6]([C:9]([O:11][CH2:57][CH2:56][CH2:61][CH3:60])=[O:10])[CH2:7][CH2:8]2)=[O:44])=[N:25][CH:26]=[CH:27][C:28]=1[S:29][C:30]1[S:34][C:33]([NH:35][C:36]2[CH:41]=[C:40]([CH3:45])[CH:39]=[CH:38][N:37]=2)=[N:32][CH:31]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10565452Tert-butyl 4-(aminomethyl)-4-phenylpiperidine-1-carboxylateHCID 592004233-Fluoro-4-(2-(pyridin-2-ylamino)thiazol-5-ylthio)picolinic acid

Product 1

HCID 86641591Butyl 4-((3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinamido)methyl)-4-phenylpiperidine-1-carboxylateYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
23 °C

Procedure

Tert-butyl 4-(aminomethyl)-4-phenylpiperidine-1-carboxylate (0.385 g, 1.325 mmol, 1.2 eq) was dissolved in NMP (10 mL) and to this solution was added 3-fluoro-4-(2-(pyridin-2-ylamino)thiazol-5-ylthio)picolinic acid (0.400 g, 1.104 mmol), EDAC (0.317 g, 1.656 mmol, 1.5 eq), HOBt (0.149 g, 1.104 mmol, 1 eq) and diisopropylethylamine (0.983 mL, 5.52 mmol, 5 eq). The resulting mixture was stirred at 23° C. for 2 days. The mixture was then diluted with 10% water/90% acetonitrile/0.05% TFA, purified on preparative HPLC (ammonium acetate/water/acetonitrile) and freeze dried to give the title compound (0.270 g, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.38 (9H, s), 1.75 (2H, ddd, J=13.5, 10.2, 3.3 Hz), 2.04-2.15 (2H, m), 2.31 (3H, s), 2.91 (2H, br s), 3.42 (2H, d, J=6.32 Hz), 3.59-3.70 (2H, m), 6.86 (1H, t, J=5.3 Hz), 6.91 (1H, s), 7.03 (1H, t, J=5.31 Hz), 7.25 (1H, t, J=7.07 Hz), 7.34-7.45 (4H, m), 7.81 (1H, s), 8.16 (1H, t, J=4.55 Hz), 8.21 (1H, d, J=5.05 Hz), 8.25 (1H, d, J=6.44 Hz), 11.78 (1H, s). LC/MS (M+H)+: 635. HPLC ret. time (Condition C): 7.033 min.

Workup

  1. custompurified on preparative HPLC (ammonium acetate/water/acetonitrile)
  2. customfreeze dried

Sources & evidence

ORD record
ord-b4fecfab0ee440778ac3e68baad0588a
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

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