N,N'-Dimethylethylenediamine → 5-ethyl-2-{4-[(1R,2R)-2-({[4-(1H-1,2,3-triazol-1-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine

HRID 1468848Notes

Reaction equation

HRID 1468848 reaction equation
Br[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][O:7][CH2:8][C@@H:9]2[CH2:11][C@@H:10]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.[NH:28]1[CH:32]=[CH:31][N:30]=[N:29]1.CC([O-])(C)C.[Na+].CNCCNC>CN1C(=O)CCC1.CCOC(C)=O.[Cu]I>[CH2:24]([C:21]1[CH:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][CH:12]([C@H:10]3[CH2:11][C@H:9]3[CH2:8][O:7][CH2:6][C:5]3[CH:26]=[CH:27][C:2]([N:28]4[CH:32]=[CH:31][N:30]=[N:29]4)=[CH:3][CH:4]=3)[CH2:13][CH2:14]2)=[N:23][CH:22]=1)[CH3:25]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 23676156Sodium t-butoxideHCID 711352722-[4-((1R,2R)-2-{[(4-bromobenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]-5-ethyl pyrimidineHCID 178418936HCID 178418936, compound

Product 1

HCID 711368025-ethyl-2-{4-[(1R,2R)-2-({[4-(1H-1,2,3-triazol-1-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The product of example 54 (step A) (100 mg, 0.232 mmol), CuI (44 mg, 0.232 mmol), triazole (48 mg, 0.697 mmol), NaOtBu (67 mg, 0.697 mmol) and N,N′-dimethylethylene diamine (61 mg, 0.697 mmol) in NMP (1 mL) was heated at 130° C. for 15 h. The reaction was cooled to room temperature, diluted with EtOAc and washed with H2O (×3). The organic layer was dried over anhydrous MgSO4, filtered, and concentrated under vacuum to leave a residue which was purified by silica gel column chromatography (elution with 2:1 hexane:ethyl acetate) to yield the title compound. MS (ESI) m/z 419 [M+H]+. GPR119 Human EC50: 0.3 nM

Workup

  1. washwashed with H2O (×3)
  2. dry with materialThe organic layer was dried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto leave a residue which
  6. customwas purified by silica gel column chromatography (elution with 2:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-f9947da1eed24c1e8911880cecf61a26
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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