Sodium hydride → 1-(5-t-butyl-2-{3-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1lambda6-[1,2,5]thiadiazolidin-2-ylmethyl]-phenyl}-2H-pyrazol-3-yl)-3-(4-fluoro-phenyl)-urea

HRID 1392323Notes

Reaction equation

HRID 1392323 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:12](=[O:13])[CH2:11][NH:10][S:9]2(=[O:15])=[O:14])=[CH:5][CH:4]=1.[H-].[Na+].[C:20]([C:24]1[CH:25]=[C:26]([NH:37][C:38]([NH:40][C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)=[O:39])[N:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35]Cl)[CH:30]=2)[N:28]=1)([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C>[C:20]([C:24]1[CH:25]=[C:26]([NH:37][C:38]([NH:40][C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)=[O:39])[N:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][N:10]3[CH2:11][C:12](=[O:13])[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:17][CH:16]=4)[S:9]3(=[O:15])=[O:14])[CH:30]=2)[N:28]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 184498681-[5-t-butyl-2-(3-chloromethyl-phenyl)-2H-pyrazol-3-yl]-3-(4-fluoro-phenyl)-ureaHCID 588428642-(4-Methoxybenzyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide

Product 1

HCID 685845351-(5-t-butyl-2-{3-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1lambda6-[1,2,5]thiadiazolidin-2-ylmethyl]-phenyl}-2H-pyrazol-3-yl)-3-(4-fluoro-phenyl)-urea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4-methoxy-benzyl)-1,1-dioxo-1λ6-[1,2,5]thiadiazolidin-3-one (64 mg, 0.25 mmol) in anhydrous DMF (2 mL) was added NaH (11 mg, 0.27 mmol) at 0° C. After stirred for 0.5 h at 0° C., a solution of 1-[5-t-butyl-2-(3-chloromethyl-phenyl)-2H-pyrazol-3-yl]-3-(4-fluoro-phenyl)-urea from the previous reaxtion (100 mg, 0.25 mmol) in anhydrous DMF (2 mL) was added to the reaction mixture, then was stirred overnight at RT. The crude was purified through prepared-HPLC to yield 1-(5-t-butyl-2-{3-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1λ6-[1,2,5]thiadiazolidin-2-ylmethyl]-phenyl}-2H-pyrazol-3-yl)-3-(4-fluoro-phenyl)-urea (45 mg). 1H NMR (DMSO-d6): 8.95 (s, 1H), 8.37 (s, 1H), 7.50-7.54 (m, 3H), 7.36-7.41 (m, 3H), 7.25 (d, J=8.8 Hz, 2H), 7.07 (t, J=8.8 Hz, 2H), 6.87 (d, J=8.4 Hz, 2H), 6.35 (s, 1H), 4.64 (s, 2H), 4.47. (s, 2H), 4.19 (s, 2H), 3.75 (s, 3H), 1.26 (s, 9H). MS (ESI) m/z: 515 (M+H+).

Workup

  1. stirringwas stirred overnight at RT
  2. customThe crude was purified through prepared-HPLC

Sources & evidence

ORD record
ord-a8b809f53c63420080127ef071db426d
Source dataset
uspto-grants-2008_03
Patent number
US07342037B2

Reaction notes

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