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

HRID 537564Notes

Reaction equation

HRID 537564 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.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 27960291-Hydroxybenzotriazole hydrateHCID 221413011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochlorideHCID 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 EDCl 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): 5182.

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-4d57e92a25fc495294018a590675dc1a
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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