3-Bromoquinoline → 9-(quinolin-3-yl)-2-((1-tosyl-1H-indol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41574

Reaction equation

HRID 41574 reaction equation
[S:1]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][C:23]3([CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[C:22]2=[O:32])=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].Br[C:34]1[CH:35]=[N:36][C:37]2[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=2.C([O-])(C)(C)C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>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].O1CCOCC1>[N:36]1[C:37]2[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:43]=[C:34]([N:29]2[CH2:30][CH2:31][C:23]3([C:22](=[O:32])[N:21]([CH2:20][C:13]4[C:14]5[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=5)[N:11]([S:1]([C:4]5[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=5)(=[O:2])=[O:3])[CH:12]=4)[CH2:26][CH2:25][CH2:24]3)[CH2:27][CH2:28]2)[CH:35]=1

Participants

7

Reactant 4

HCID 214133-BromoquinolineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 672515122-((1-tosyl-1H-indol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-one

Product 1

HCID 672511379-(quinolin-3-yl)-2-((1-tosyl-1H-indol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-oneYield 72.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The mixture of 2-((1-tosyl-1H-indol-3-yl)methyl)-2,9-diazaspiro[5.5]undecan-1-one (100 mg, 0.15 mmol, contains 1.7 moleq TFA), 3-bromoquinoline (49 mg, 0.23 mmol), Pd2dba3 (7 mg, 7.7 μmol), sodium t-butanolate (45 mg, 0.46 mmol), 2-(2-dicyclohexylphosphanylphenyl)-N,N-dimethylaniline (DavePhos, 6.1 mg, 0.015 mmol) and dry dioxane (2 mL) was placed in a microwave tube and flushed with argon. The tube was sealed and the suspension was heated at 100° C. for 1 h under microwave conditions. The reaction mixture was diluted with ethyl acetate and washed with water and brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting brown oil was purified by flash chromatography (EtOAc/heptane 3:1) to yield the title compound (63 mg, 68%). [LCMS RtA=1.31 min, [M+H]+=579.2].

Workup

  1. customwas placed in a microwave tube
  2. customflushed with argon
  3. customThe tube was sealed
  4. additionThe reaction mixture was diluted with ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting brown oil was purified by flash chromatography (EtOAc/heptane 3:1)

Sources & evidence

ORD record
ord-54e8e8e4441743bbb73db5a0c3ee97d0
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Linked notes

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