Cyclopentylamine → HCID 67435793, compound

HRID 1663585Notes

Reaction equation

HRID 1663585 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[CH:33]=[CH:32][C:31](Cl)=[CH:30][CH:29]=2)[N:9]2[CH2:13][CH2:12][C@@H:11]([NH:14][C:15](=[O:27])[C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[CH2:10]2)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=2[N:54](C)C)CCCCC1.[CH:63]1([NH2:68])[CH2:67][CH2:66][CH2:65][CH2:64]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1CCCC1>C(OCC)(=O)C.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].O>[CH:63]1([NH:68][C:2]2[CH:7]=[CH:6][C:5]([CH:8]([C:28]3[CH:33]=[CH:32][C:31]([NH:54][CH:49]4[CH2:50][CH2:51][CH2:52][CH2:53]4)=[CH:30][CH:29]=3)[N:9]3[CH2:13][CH2:12][C@@H:11]([NH:14][C:15](=[O:27])[C:16]4[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=4)[CH2:10]3)=[CH:4][CH:3]=2)[CH2:67][CH2:66][CH2:65][CH2:64]1

Participants

8

Reactant 4

HCID 2906CyclopentylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23714775LiHMDS tetrahydrofuranHCID 67436302HCID 67436302, compound

Product 1

HCID 67435793HCID 67435793, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of the compound obtained in Example 1 (50 mg), tris(dibenzylideneacetone)dipalladium (0.9 mg), 2-(dicyclohexylphosphino)-2′-(N,N-dimethylamino)biphenyl (1.5 mg), cyclopentylamine (24 μL) and 1.0M lithium bis(trimethylsilyl)amide/tetrahydrofuran (0.35 mL) was stirred at 110° C. for 10 minutes by using Microwave Synthetic System (Discover; CEM Ltd.). The reaction mixture was diluted with ethyl acetate and thereto was added water. The organic layer was separated and evaporated in vacuo. The residue was purified by HPLC (XTerra Prep MS C18 column; Waters Inc., solvent; water/methanol=1:1→5:95), dissolved in tert-buthanol and lyophilized to give (3R)-1-[bis-[4-(cyclopentylamino)phenyl]methyl]-3-[[4-(trifluoromethoxy)benzoyl]amino]pyrrolidine (18.7 mg, yield: 32%) as a powder.

Workup

  1. customThe organic layer was separated
  2. customevaporated in vacuo
  3. customThe residue was purified by HPLC (XTerra Prep MS C18 column; Waters Inc., solvent; water/methanol=1:1→5:95)
  4. dissolutiondissolved in tert-buthanol

Sources & evidence

ORD record
ord-11644238c03344a3ae12fa857474620a
Source dataset
uspto-grants-2011_10
Patent number
US08034949B2

Reaction notes

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