Triethylamine → 1-(3-hydroxyazetidin-1-yl)-2-(4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)ethanone

HRID 1474663Notes

Reaction equation

HRID 1474663 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C@H:16]3[CH2:18][C@H:17]3[CH2:19][CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][C:29]([OH:31])=O)=[CH:24][CH:23]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1.O.ON1C2C=CC=CC=2N=N1.Cl.[OH:44][CH:45]1[CH2:48][NH:47][CH2:46]1.Cl.C(/N=N/CCCN(C)C)C.C(N(CC)CC)C>C(Cl)Cl.CCOC(C)=O.CO>[OH:44][CH:45]1[CH2:48][N:47]([C:29](=[O:31])[CH2:28][C:25]2[CH:24]=[CH:23][C:22]([O:21][CH2:20][CH2:19][C@@H:17]3[CH2:18][C@@H:16]3[CH:13]3[CH2:14][CH2:15][N:10]([C:7]4[N:6]=[CH:5][C:4]([CH2:3][O:2][CH3:1])=[CH:9][N:8]=4)[CH2:11][CH2:12]3)=[CH:27][CH:26]=2)[CH2:46]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 89583857(4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)acetic acidHCID 178465607HCID 178465607, compound

Product 1

HCID 895838601-(3-hydroxyazetidin-1-yl)-2-(4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)ethanone

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)acetic acid (70 mg, 0.165 mmol), 1-hydroxybenzotriazole hydrate (37.8 mg, 0.247 mmol), 3-hydroxyazetidine hydrochloride (27 mg, 0.247 mmol) and (E)-3-(ethyldiazenyl)-N,N-dimethylpropan-1-amine hydrochloride (44.3 mg, 0.247 mmol) were dissolved in CH2Cl2 (4 ml). The mixture was stirred at RT for 5 min. and triethylamine (0.078 ml, 0.556 mmol) added. The mixture was stirred at RT overnight and the mixture loaded directly onto a preparative TLC plate that was developed with 10% MeOH in EtOAc. The desired product (Rf=0.35 @ 10% MeOH in EtOAc) was collected to give the title compound. 1H NMR (500 MHz, CDCl3) δ 8.30 (s, 2H), 7.20 (d, 2H), 6.85 (d, 2H), 4.70 (m, 2H), 4.55 (broad, s, 1H), 4.22 (s, 2H), 4.10 (m, 1H), 4.05 (m, 2H), 3.85 (m, 2H), 3.40 (s, 2H), 3.35 (s, 3H), 2.85 (m, 2H), 2.05 (m, 1H), 1.95 (m, 2H), 1.55 (m, 1H), 1.38 (m, 2H), 1.10 (m, 1H), 0.95 (m, 1H), 0.68 (m, 2H), −0.40 (m, 1H). LC/MS (m/z): 481 (M+H)+, GPR119 Human EC50: 7.7 nM.

Workup

  1. stirringThe mixture was stirred at RT overnight
  2. customThe desired product (Rf=0.35 @ 10% MeOH in EtOAc) was collected

Sources & evidence

ORD record
ord-c9d6c1f446cc4a59837b2c74277a9c36
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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