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

HRID 1474701Notes

Reaction equation

HRID 1474701 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=O)=[C:22]([F:30])[CH:21]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[NH:31]1[CH2:34][CH2:33][CH2:32]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:31]1([C:27](=[O:29])[CH2:26][C:23]2[CH:24]=[CH:25][C:20]([O:19][CH2:18][CH2:17][C@@H:15]3[CH2:16][C@@H:14]3[CH:11]3[CH2:10][CH2:9][N:8]([C:5]4[N:6]=[CH:7][C:2]([Cl:1])=[CH:3][N:4]=4)[CH2:13][CH2:12]3)=[CH:21][C:22]=2[F:30])[CH2:34][CH2:33][CH2:32]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 89583888[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid

Product 1

HCID 895840021-(azetidin-1-yl)-2-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-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-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid (100 mg, 0.230 mmol) in 1 ml of anhydrous DMF at RT was added azetidine (13.2 mg, 0.230 mmol) and N,N-diisopropylethylamine (0.201 ml, 1.15 mmol). o-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (175 mg, 0.461 mmol) was added to the solution and the mixture stirred at RT for 4 hrs. The mixture was filtered and purified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 35-75% acetonitrile in 0.1% formic acid in water gradient) to give the title compound. LC/MS (m/z): 473.1 (M+H)+. GPR119 Human EC50: 0.19 nM

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 35-75% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-5a1abd22f25b411b83e32254ca48999e
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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