1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68157476, compound

HRID 537539Notes

Reaction equation

HRID 537539 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[F:10][C:11]([F:38])([F:37])[C:12]1[CH:13]=[N:14][N:15]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][CH:24]([C:28]3[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=3)[CH2:25][CH2:26][CH3:27])=[CH:19][CH:18]=2)[CH:16]=1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.C(N=C=NCCCN(C)C)C>O1CCCC1>[F:37][C:11]([F:10])([F:38])[C:12]1[CH:13]=[N:14][N:15]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][CH:24]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([NH:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:33])=[CH:35][CH:36]=3)[CH2:25][CH2:26][CH3:27])=[CH:19][CH:18]=2)[CH:16]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68157668HCID 68157668, compound

Product 1

HCID 68157476HCID 68157476, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl 3-aminopropanoate hydrochloride (418 mg, 2.72 mmol), 4-(1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenylamino)butyl)benzoic acid (732 mg, 1.82 mmol), 1-hydroxybenzotriazole hydrate (292 mg, 1.91 mmol), and N,N-diisopropylethylamine (1.20 mL, 7.26 mmol) in tetrahydrofuran (18.2 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (557 mg, 2.90 mmol). The mixture was stirred for 48 hours at ambient temperature. The reaction mixture was concentrated and the crude material was purified by column chromatography (0-100% ethyl acetate in heptane) to afford racemic ethyl 3-(4-(1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenylamino)butyl)benzamido)propanoate (684 mg, 85%) as a solid. The racemate was further purified via chiral SFC to afford 300 mg of Isomer 1 and 300 mg of Isomer 2, which were used in conversion to the final enatiopure products. 1H NMR (400 MHz, CDCl3, δ): 7.94 (q, J=0.8 Hz, 1H), 7.81 (s, 1H), 7.73 (d, J=8.2 Hz, 2H), 7.39 (d, J=8.2 Hz, 2H), 7.32 (d, J=9.0 Hz, 2H), 6.84 (t, J=5.8 Hz, 1H), 6.53 (d, J=8.8 Hz, 2H), 4.42-4.34 (m, 1H), 4.31 (d, J=4.7 Hz, 1H), 4.16 (q, J=7.2 Hz, 2H), 3.71 (q, J=6.1 Hz, 2H), 2.63 (t, J=5.9 Hz, 2H), 1.88-1.71 (m, 2H), 1.53-1.31 (m, 2H), 1.27 (t, J=7.0 Hz, 3H), 0.95 (t, J=7.3 Hz, 3H). Chiral SFC: Chiralpak AD-H, 10×250 mm; Mobile Phase 65:35 CO2/methanol, 65 mL/min, Retention time: 3.95 min (Isomer 1), 6.81 min (Isomer 2).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe crude material was purified by column chromatography (0-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-75155c5ff97c41c3b561a44b73f55736
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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