Sodium t-butoxide → (S)-1'-(5-ethylpyrimidin-2-yl)-3-((6-fluoro-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)amino)-[1,4'-bipiperidin]-2-one

HRID 407965Notes

Reaction equation

HRID 407965 reaction equation
Br[C:2]1[C:12]([F:13])=[CH:11][C:5]2[S:6](=[O:10])(=[O:9])[CH2:7][CH2:8][C:4]=2[CH:3]=1.[NH2:14][C@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([CH:21]2[CH2:26][CH2:25][N:24]([C:27]3[N:32]=[CH:31][C:30]([CH2:33][CH3:34])=[CH:29][N:28]=3)[CH2:23][CH2:22]2)[C:16]1=[O:35].CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:33]([C:30]1[CH:29]=[N:28][C:27]([N:24]2[CH2:23][CH2:22][CH:21]([N:17]3[CH2:18][CH2:19][CH2:20][C@H:15]([NH:14][C:2]4[C:12]([F:13])=[CH:11][C:5]5[S:6](=[O:10])(=[O:9])[CH2:7][CH2:8][C:4]=5[CH:3]=4)[C:16]3=[O:35])[CH2:26][CH2:25]2)=[N:32][CH:31]=1)[CH3:34]

Participants

5

Reactant 3

HCID 23676156Sodium t-butoxideHCID 674697205-Bromo-6-fluoro-2,3-dihydrobenzo[b]thiophene 1,1-dioxideHCID 67470426(S)-3-amino-1'-(5-ethylpyrimidin-2-yl)-1,4'-bipiperidin-2-one

Product 1

HCID 86688107(S)-1'-(5-ethylpyrimidin-2-yl)-3-((6-fluoro-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)amino)-[1,4'-bipiperidin]-2-oneYield 31.9%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

A flask was charged with 5-bromo-6-fluoro-2,3-dihydrobenzo[b]thiophene 1,1-dioxide (0.070 g, 0.26 mmol), (S)-3-amino-1′-(5-ethylpyrimidin-2-yl)-[1,4′-bipiperidin]-2-one (Steps A-C, 0.05 g, 0.16 mmol), Pd2 dba3 (0.0075 g, 0.0082 mmol), Binap-rac (0.0010 g, 0.0016 mmol), sodium t-butoxide (0.033 g, 0.35 mmol), and degassed toluene (3 mL). The reaction was stirred at 90° C. for 4 hours. The organic solvent was removed under reduced pressure. The residue was purified using silica gel column chromatography with 50-100% ethyl acetate, followed by preparative TLC using 2% methanol in ethyl acetate to provide (S)-1′-(5-ethylpyrimidin-2-yl)-3-((6-fluoro-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)amino)-[1,4′-bipiperidin]-2-one (0.025 g, 0.051 mmol, 31% yield) as off white solid. Mass spectrum (apci) m/z=488.3 (M+H).

Workup

  1. customdegassed toluene (3 mL)
  2. customThe organic solvent was removed under reduced pressure
  3. customThe residue was purified

Sources & evidence

ORD record
ord-22b2a5aef6c540f9bb36ef37c946eb0c
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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