Azetidine → 4-[(1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)phenoxy]ethyl}cyclopropyl]-1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]piperidine

HRID 1850778Notes

Reaction equation

HRID 1850778 reaction equation
[CH:1]([C:4]1[N:8]=[C:7]([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]([OH:30])=O)=[CH:23][CH:22]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)([CH3:3])[CH3:2].O.O[N:33]1[C:37]2C=CC=[CH:41][C:36]=2N=N1.Cl.C(/N=N/CCCN(C)C)C.N1CCC1>C(Cl)Cl.CO>[N:33]1([C:28](=[O:30])[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[CH2:13][CH2:14][N:9]([C:7]4[O:6][N:5]=[C:4]([CH:1]([CH3:2])[CH3:3])[N:8]=4)[CH2:10][CH2:11]3)=[CH:22][CH:23]=2)[CH2:41][CH2:36][CH2:37]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 708186952-(4-(2-((1S,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)ethoxy)phenyl)acetic acidHCID 178465607HCID 178465607, compound

Product 1

HCID 708559784-[(1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)phenoxy]ethyl}cyclopropyl]-1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]piperidine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

2-(4-(2-((1S,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)ethoxy)phenyl)acetic acid (100 mg, 0.242 mmol), 1-hydroxybenzotriazole hydrate (55 mg, 0.363 mmol), and (E)-3-(ethyldiazenyl)-N,N-dimethylpropan-1-amine hydrochloride (70.0 mg, 0.363 mmol) were dissolved in CH2Cl2 (4 ml). The mixture was stirred at RT for 5 min. and azetidine (21 mg, 0.363 mmol) was added. The mixture was stirred at RT overnight and loaded directly on Preparative TLC that was developed with 5% MeOH in DCM. The desired product (Rf=0.35 @ 5% MeOH in DCM) was collected to give the title compound. 1H NMR (500 MHz, CDCl3) δ 7.20 (d, 2H), 6.90 (d, 2H), 4.05-4.15 (m, 8H), 3.41 (s, 2H), 3.05 (m, 2H), 2.96 (m, 1H), 2.26 (m, 2H), 2.18 (m, 1H), 1.95 (m, 2H), 1.50 (m, 3H), 1.35 (d, 6H), 0.95-1.05 (m, 2H), 0.68 (m, 2H), −0.40 (m, 1H). LC/MS (m/z): 453 (M+H)+, GPR119 Human EC50: 1.8 nM.

Workup

  1. stirringThe mixture was stirred at RT overnight
  2. customThe desired product (Rf=0.35 @ 5% MeOH in DCM) was collected

Sources & evidence

ORD record
ord-b673f4d15d3e4a7fb8fb7fad40482f5a
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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