Sodium Carbonate → 3-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide

HRID 1800830Notes

Reaction equation

HRID 1800830 reaction equation
[F:1][C:2]1[C:3]([C:22]([NH:24][CH2:25][C:26]2([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:31][CH2:30][N:29](C(OCCCC)=O)[CH2:28][CH2:27]2)=[O:23])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=2)=[N:11][CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+]>FC(F)(F)C(O)=O.ClCCl>[F:1][C:2]1[C:3]([C:22]([NH:24][CH2:25][C:26]2([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]2)=[O:23])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=2)=[N:11][CH:10]=1

Participants

4

Reactant 2

HCID 10340Sodium CarbonateHCID 86641591Butyl 4-((3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinamido)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 250328563-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamideYield 70%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
23 °C

Procedure

Tert-butyl 4-((3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinamido)methyl)-4-phenylpiperidine-1-carboxylate (˜1.80 g, ˜2.84 mmol, described in Example 1) was dissolved in trifluoroacetic acid/dichloromethane (1:5, mL). This mixture was stirred at 23° C. for 2 hours, then neutralized with sat. sodium carbonate to pH˜7. The aqueous phase was then extracted with ethyl acetate/THF and the combined organic layers were dried over anhydrous magnesium sulfate to give the title material (1.06 g, 70%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.99-2.09 (2H, m), 2.28 (2H, br s), 2.31 (3H, s), 2.66-2.82 (2H, m), 3.25 (2H, m), 3.45 (2H, br d), 6.86 (1H, d, J=5.31 Hz), 6.93 (1H, s), 7.05 (1H, t, J=5.18 Hz), 7.26-7.34 (1H, m), 7.38-7.46 (4H, m), 7.81 (1H, s), 8.17 (1H, d, J=5.31 Hz), 8.23 (1H, d, J=5.05 Hz), 8.37 (1H, t, J=6.44 Hz), 11.84 (1H, s). LC/MS (M+H)+: 535. HPLC ret. time (Condition C): 4.085 min.

Workup

  1. extractionThe aqueous phase was then extracted with ethyl acetate/THF
  2. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate

Sources & evidence

ORD record
ord-b0266344475f4522a1d09c8983d5e768
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

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