Triethylamine → 2-[2,6-difluoro-4-(2-{(1S,2R)-2-[1-(5-methoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]-1-(3-hydroxyazetidin-1-yl)ethanone

HRID 1474723Notes

Reaction equation

HRID 1474723 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]3[N:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=3)[CH2:16][CH2:15]2)[CH:5]=[C:4]([F:28])[C:3]=1[CH2:29][C:30](O)=[O:31].O.ON1C2C=CC=CC=2N=N1.Cl.[OH:45][CH:46]1[CH2:49][NH:48][CH2:47]1.Cl.C(/N=N/CCCN(C)C)C.C(N(CC)CC)C>C(Cl)Cl>[F:28][C:4]1[CH:5]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]3[N:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=3)[CH2:16][CH2:15]2)[CH:7]=[C:2]([F:1])[C:3]=1[CH2:29][C:30]([N:48]1[CH2:49][CH:46]([OH:45])[CH2:47]1)=[O:31]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 1176784882-(2,6-difluoro-4-(2-((1S,2R)-2-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethoxy)phenyl)acetic acidHCID 178465607HCID 178465607, compound

Product 1

HCID 895820562-[2,6-difluoro-4-(2-{(1S,2R)-2-[1-(5-methoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]-1-(3-hydroxyazetidin-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(2,6-difluoro-4-(2-((1S,2R)-2-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethoxy)phenyl)acetic acid (80 mg, 0.179 mmol), 1-hydroxybenzotriazole hydrate (41.1 mg, 0.268 mmol), 3-hydroxyazetidine hydrochloride (29.4 mg, 0.268 mmol) and (E)-3-(ethyldiazenyl)-N,N-dimethylpropan-1-amine hydrochloride (48.2 mg, 0.268 mmol) were dissolved in CH2Cl2 (4 ml). The mixture was stirred at RT for 5 min and triethylamine (0.075 ml, 0.536 mmol) was added. The mixture was stirred at RT overnight and purified by loading directly onto a Preparative TLC plate that was developed with pure EtOAc. The desired product (Rf=0.40 @ pure EtOAc) was collected to give the title compound. 1H NMR (500 MHz, CDCl3) δ 8.15 (s, 2H), 6.50 (d, 2H), 4.60 (m, 3H), 4.40 (m, 1H), 4.30 (m, 1H), 4.05 (m, 2H), 3.90 (m, 11-1), 3.80 (s, 3H), 3.41 (s, 2H), 3.05 (broad, s, 1H), 2.85 (m, 2H), 2.15 (m, 1H), 1.92 (m, 2H), 1.55 (m, 1H), 1.40 (m, 2H), 0.95 (m, 2H), 0.68 (m, 2H), −0.40 (m, 1H). LC/MS (m/z): 503 (M+H)+, GPR119 Human EC50: 0.59 nM.

Workup

  1. stirringThe mixture was stirred at RT overnight
  2. custompurified by loading directly onto a Preparative TLC plate that
  3. customThe desired product (Rf=0.40 @ pure EtOAc) was collected

Sources & evidence

ORD record
ord-9ae6b6af2a2b49dd9387a558a4cde311
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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