Diisopropylethylamine → 2-(4-{2-[(1S,2R)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}-2-fluorophenyl)-1-(3-hydroxyazetidin-1-yl)ethanone

HRID 1474706Notes

Reaction equation

HRID 1474706 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[CH:6]=[N:7][C:8]([N:11]2[CH2:16][CH2:15][CH:14]([C@H:17]3[CH2:19][C@H:18]3[CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][C:26]([CH2:29][C:30](O)=[O:31])=[C:25]([F:33])[CH:24]=3)[CH2:13][CH2:12]2)=[N:9][CH:10]=1)[CH3:2].Cl.[OH:35][CH:36]1[CH2:39][NH:38][CH2:37]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][CH2:4][C:5]1[CH:10]=[N:9][C:8]([N:11]2[CH2:16][CH2:15][CH:14]([C@H:17]3[CH2:19][C@H:18]3[CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][C:26]([CH2:29][C:30]([N:38]4[CH2:39][CH:36]([OH:35])[CH2:37]4)=[O:31])=[C:25]([F:33])[CH:24]=3)[CH2:13][CH2:12]2)=[N:7][CH:6]=1)[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89582003(4-{2-[(1S,2R)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}-2-fluorophenyl)acetic acid

Product 1

HCID 895840212-(4-{2-[(1S,2R)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}-2-fluorophenyl)-1-(3-hydroxyazetidin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-{2-[(1S,2R)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}-2-fluorophenyl)acetic acid (50, 0.109 mmol) and 3-hydroxy azetidine hydrochloride (11.97 mg, 0.109 mmol) were dissolved in DMF (1 ml) and HATU (83 mg, 0.219 mmol) and DIEA (0.057 ml, 0.328 mmol) added. The mixture was stirred at RT for 2 hr. The mixture was diluted with ethyl acetate (20 mL), washed with brine, dried over MgSO4, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, Biotage 25M, using a gradient eluant of MeOH/DCM (0-10%) to to provide the title compound. LC/MS (m/z): 513 (M+H)+. GPR119 Human EC50: 1.9 nM

Workup

  1. washwashed with brine
  2. dry with materialdried over MgSO4
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was purified by column chromatography on silica gel, Biotage 25M

Sources & evidence

ORD record
ord-86356b48810c49159981d55ea537577a
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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