Water → HCID 86717805, compound

HRID 1468875Notes

Reaction equation

HRID 1468875 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:28][C:29]([OH:31])=O)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][C@@H:11]1[CH2:13][C@@H:12]1[CH:14]1[CH2:19][CH2:18][N:17]([C:20]2[O:24][N:23]=[C:22]([CH:25]([CH3:27])[CH3:26])[N:21]=2)[CH2:16][CH2:15]1.C1C=CC2N(O)N=NC=2C=1.O.C[CH2:44][N:45]=[C:46]=NCCCN(C)C.Cl.Cl.CNC>C(Cl)Cl.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH2:28][C:29]([N:45]([CH3:46])[CH3:44])=[O:31])[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][C@@H:11]1[CH2:13][C@@H:12]1[CH:14]1[CH2:15][CH2:16][N:17]([C:20]2[O:24][N:23]=[C:22]([CH:25]([CH3:26])[CH3:27])[N:21]=2)[CH2:18][CH2:19]1

Participants

8

Reactant 5

HCID 962WaterHCID 10473Dimethylamine, hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86717804HCID 86717804, compound

Product 1

HCID 86717805HCID 86717805, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(3-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)acetic acid (Step D product, 60 mg, 0.139 mmol), HOBT.H2O (32 mg, 0.209 mmol), and EDC.HCl (40 mg, 0.209 mmol) dissolved in DCM (1 mL) was stirred at rt for 30 min. Dimethylamine hydrochloride (35 mg, 0.431 mmol) was added to this solution and the reaction aged at rt for 3 hrs. The reaction mixture was then diluted with DCM (1 mL) and the residue loaded directly onto 2×2000 micron silica preparative TLC plates (uv 254 active) which were developed using 100% EtOAc as the solvent system. The desired silica (Rf=0.4 @ 100% EtOAc) was collected and extracted to give the title compound (37 mg, 58%). 1H NMR (500 MHz, CD3CN) δ 7.37 (t, 1H), 7.06 (d, 1H), 6.99 (d, 1H), 4.52 (q, 2H), 3.99 (dd, 2H), 3.69 (s, 2H), 3.64 (q, 1H), 3.27 (t, 1H), 3.02 (s, 3H), 3.01-2.90 (m, 2H), 2.88 (s, 3H), 2.84 (t, 1H), 1.94 (d, 1H), 1.78 (d, 1H), 1.41-1.26 (m, 2H), 1.23 (s, 6H), 1.20-1.14 (m, 1H), 1.06-0.96 (m, 1H), 0.77 (p, 2H), 0.02 (q, 1H). LC/MS (m/z): 459 (M+H)+, GPR119 Human EC50: 1.6 nM.

Workup

  1. waitthe reaction aged at rt for 3 hrs
  2. customThe desired silica (Rf=0.4 @ 100% EtOAc) was collected
  3. extractionextracted

Sources & evidence

ORD record
ord-28ac8ab3f06c4649bde36ff74f908bac
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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