Azetidine → 1-(azetidin-1-yl)-2-[4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]ethanone

HRID 1474712Notes

Reaction equation

HRID 1474712 reaction equation
[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[C:23]([F:31])[CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].[NH:32]1[CH2:35][CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:32]1([C:28](=[O:29])[CH2:27][C:24]2[CH:25]=[CH:26][C:21]([O:20][CH2:19][CH2:18][C@@H:16]3[CH2:17][C@@H:15]3[CH:12]3[CH2:11][CH2:10][N:9]([C:6]4[N:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][N:5]=4)[CH2:14][CH2:13]3)=[CH:22][C:23]=2[F:31])[CH2:35][CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89584013[4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid

Product 1

HCID 1176785301-(azetidin-1-yl)-2-[4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]ethanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid (20.0 mg, 0.047 mmol) in 1 ml anhydrous DMF at RT was added azetidine (4.01 mg, 0.070 mmol) and N,N-diisopropylethylamine (0.201 ml, 1.15 mmol). o-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (30.2 mg, 0.234 mmol) was added and the mixture stirred at RT for 4 hrs. The mixture was filtered and purified by reversed-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 45-90% acetonitrile in 0.1% formic acid in water gradient) to afford the title compound. LC/MS (m/z): 467.2 (M+H)+. GPR119 Human EC50: 0.40 nM.

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by reversed-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 45-90% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-16fdbf6226224a8fafe5005ed9df52c4
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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