Diisopropylethylamine → ethyl 3-(4-(1-(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzamido)propanoate

HRID 1520943Notes

Reaction equation

HRID 1520943 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:10][C:11]1[CH:30]=[C:29]([N:31]2[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[N:32]2)[CH:28]=[CH:27][C:12]=1[O:13][CH:14]([C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=1)[CH2:15][CH2:16][CH3:17].C1C=C2N=NN(O)C2=CC=1.O.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>C(OCC)(=O)C.C1COCC1>[CH3:10][C:11]1[CH:30]=[C:29]([N:31]2[CH:35]=[C:34]([C:36]([F:37])([F:39])[F:38])[CH:33]=[N:32]2)[CH:28]=[CH:27][C:12]=1[O:13][CH:14]([C:18]1[CH:19]=[CH:20][C:21]([C:22]([NH:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:23])=[CH:25][CH:26]=1)[CH2:15][CH2:16][CH3:17]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 681566274-(1-(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoic acid

Product 1

HCID 68156556ethyl 3-(4-(1-(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzamido)propanoateYield 53.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of ethyl 3-aminopropanoate hydrochloride (46 mg, 0.3 mmol), 4-(1-(2-methyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoic acid (84 mg, 0.2 mmol), HOBt hydrate (34 mg, 0.22 mmol), and DIPEA (0.133 ml, 0.8 mmol), and THF (3 ml) was added EDCI hydrochloride (62 mg, 0.32 mmol) in one portion at the ambient temperature and the reaction was stirred at the same temperature for three days. The mixture was diluted with 3 ml of ethyl acetate, 3 ml of heptanes, and washed successively with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and loaded on silica gel. Chromatography on a silica gel column, eluting with a gradient from 10% to 50% of ethyl acetate in heptane gave the target product as a colorless gum (55 mg, 53%). 1H NMR (500 MHz, CDCl3) δ 8.01 (s, 1H), 7.84 (s, 1H), 7.75 (d, J=8.29 Hz, 2H), 7.45 (d, J=2.68 Hz, 1H), 7.40 (d, J=8.05 Hz, 2H), 7.20 (dd, J=2.68, 8.78 Hz, 1H), 6.81-6.87 (m, 1H), 6.61 (d, J=8.78 Hz, 1H), 5.21 (dd, J=5.12, 7.56 Hz, 1H), 4.18 (q, J=7.16 Hz, 2H), 3.73 (q, J=6.02 Hz, 2H), 2.64 (t, J=5.85 Hz, 2H), 2.40 (s, 3H), 2.00-2.10 (m, 1H), 1.81-1.90 (m, 1H), 1.52-1.61 (m, 1H), 1.44-1.51 (m, 1H), 1.28 (t, J=7.20 Hz, 3H), 0.98 (t, J=7.44 Hz, 3H). MS (M+1): 518.2.

Workup

  1. washwashed successively with saturated aqueous sodium bicarbonate and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. washChromatography on a silica gel column, eluting with a gradient from 10% to 50% of ethyl acetate in heptane

Sources & evidence

ORD record
ord-d3f59e4437194ccc963cac8e1df3ad33
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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