Diisopropylethylamine → HCID 70558977, compound

HRID 2278795Notes

Reaction equation

HRID 2278795 reaction equation
[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:27]=[C:26]([CH3:28])[C:20]([O:21][CH2:22][CH2:23][CH2:24][NH2:25])=[C:19]([CH2:29][CH3:30])[CH:18]=4)[N:13]=3)[CH:9]=[C:8]([O:31][CH3:32])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:33]([O:35][C:36](=[O:41])[CH2:37][C:38]([O-])=[O:39])[CH3:34].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CC(=O)OCC>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:27]=[C:26]([CH3:28])[C:20]([O:21][CH2:22][CH2:23][CH2:24][NH:25][C:38](=[O:39])[CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:41])=[C:19]([CH2:29][CH3:30])[CH:18]=4)[N:13]=3)[CH:9]=[C:8]([O:31][CH3:32])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 3595298Propanedioic acid, monoethyl esterHCID 70558665HCID 70558665, compound

Product 1

HCID 70558977HCID 70558977, compoundYield 118.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)propan-1-amine (200 mg, 0.458 mmol), monoethylmalonate (91 mg, 0.687 mmol) and DIPEA (178 mg, 1.37 mmol) in DMF (5 mL) is added TBTU (191 mg, 0.596 mmol). The mixture is stirred at rt for 18 h. The solution is diluted with EA (50 mL) and washed twice with sat aq. NaHCO3 solution (50 mL) followed by brine (50 mL). The org. extract is dried over Na2SO4, filtered and concentrated to give crude ethyl 3-((3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy) propyl)amino)-3-oxopropanoate (298 mg) as a yellow oil; LC-MS: tR=1.19 min, [M+H]+=551.38. This material is dissolved in methanol (2 mL), THF (2 mL) and 2 N aq. LiOH (1 mL). The solution is stirred at rt for 2 h before it is concentrated, diluted with DCM (20 mL) and washed with 2 N aq. HCl (10 mL). The aq. phase is extracted three times with DCM (3×20 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (105 mg) as a white solid; LC-MS: tR=1.14 min, [M+H]+=523.21; 1H NMR (CD3OD): δ 7.82 (s, 1H), 7.79 (s, 1H), 7.49 (s, 1H), 7.23 (s, 1H), 3.99 (s, 3H), 3.92 (t, J=6.2 Hz, 2H), 3.52 (t, J=6.9 Hz, 2H), 3.31 (s, 2H), 3.22-3.31 (m, 1H), 2.75 (q, J=7.5 Hz, 2H), 2.36 (s, 3H), 2.04-2.15 (m, 4H), 1.85-1.95 (m, 4H), 1.73-1.82 (m, 2H), 1.29 (t, J=7.5 Hz, 3H).

Workup

  1. washwashed twice with sat aq. NaHCO3 solution (50 mL)
  2. extractionextract
  3. dry with materialis dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c51e167684f44aa0bea827a115728fcc
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

Loading…