Triethylamine → cyclopropylmethyl-4-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-3-fluorophenoxy]ethyl}cyclopropyl)piperidine-1-carboxylate

HRID 1850764Notes

Reaction equation

HRID 1850764 reaction equation
[N:1]1([C:5](=[O:26])[CH2:6][C:7]2[CH:24]=[CH:23][C:10]([O:11][CH2:12][CH2:13][C@@H:14]3[CH2:16][C@@H:15]3[CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:9][C:8]=2[F:25])[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[C:34](=O)([O:40]N1C(=O)CCC1=O)[O:35][CH2:36][CH:37]1[CH2:39][CH2:38]1>ClCCl.[NH4+].[Cl-]>[CH:37]1([CH2:36][O:35][C:34]([N:20]2[CH2:19][CH2:18][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][O:11][C:10]3[CH:23]=[CH:24][C:7]([CH2:6][C:5]([N:1]4[CH2:4][CH2:3][CH2:2]4)=[O:26])=[C:8]([F:25])[CH:9]=3)[CH2:22][CH2:21]2)=[O:40])[CH2:39][CH2:38]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 57747023Cyclopropylmethyl 2,5-dioxopyrrolidin-1-yl carbonateHCID 708563224-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-3-fluorophenoxy]ethyl)cyclopropyl)piperidine

Product 1

HCID 70856274cyclopropylmethyl-4-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-3-fluorophenoxy]ethyl}cyclopropyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a stirred solution of 4-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-3-fluorophenoxy]ethyl)cyclopropyl)piperidine (Step B, Example 11; 0.30 g, 0.93 mmol) in dichloromethane (4.6 mL) under a nitrogen atmosphere was added triethylamine (0.36 mL, 2.6 mmol) and cyclopropylmethyl 2,5-dioxopyrrolidin-1-yl carbonate (0.35 g, 1.67 mmol). The resulting solution was stirred for 18 h at ambient temperature. The solution was diluted with saturated NH4Cl(aq.) (10 mL). The resulting layers were separated and the aqueous phase extracted with dichloromethane (2×30 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the obtained residue by CombiFlash chromatography (12 g silica gel, 0 to 25% EtOAc in heptane) provided the title compound as an off white semi-solid. LC/MS (m/z): 459.3 (M+H)+. GPR119 Human EC50: 2.0 nM.

Workup

  1. customThe resulting layers were separated
  2. extractionthe aqueous phase extracted with dichloromethane (2×30 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the obtained residue by CombiFlash chromatography (12 g silica gel, 0 to 25% EtOAc in heptane)

Sources & evidence

ORD record
ord-345ade8f6a6b415c9f5ab7fef37ad50a
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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