Diisopropylethylamine → 1-{2-[((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl]-4-(trifluoromethyl)phenyl}-3-ethylurea

HRID 1374289Notes

Reaction equation

HRID 1374289 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]2[CH2:12][CH2:11][C@@H:10]([N:13]([CH:15]([CH3:17])[CH3:16])[CH3:14])[CH2:9][C@H:8]2[CH2:18][CH2:19][CH3:20])[C:3]1=[O:21].C(N(CC)C(C)C)(C)C.[CH2:31]([NH:33][C:34](=[O:49])[NH:35][C:36]1[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][C:37]=1[C:38](O)=[O:39])[CH3:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:15]([N:13]([CH3:14])[C@@H:10]1[CH2:11][CH2:12][C@H:7]([N:4]2[CH2:5][CH2:6][C@H:2]([NH:1][C:38]([C:37]3[CH:41]=[C:42]([C:45]([F:47])([F:48])[F:46])[CH:43]=[CH:44][C:36]=3[NH:35][C:34]([NH:33][CH2:31][CH3:32])=[O:49])=[O:39])[C:3]2=[O:21])[C@H:8]([CH2:18][CH2:19][CH3:20])[CH2:9]1)([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222687522-(3-Ethylureido)-5-(trifluoromethyl)benzoic acidHCID 68767742(S)-3-amino-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)pyrrolidin-2-one

Product 1

HCID 687670491-{2-[((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl]-4-(trifluoromethyl)phenyl}-3-ethylurea

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-3-amino-1-[(1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl]pyrrolidin-2-one (77 mg, 0.26 mmol) in DMF (2 mL) was added N,N-diisopropylethylamine (0.32 mL), 2-(3-ethylureido)-5-(trifluoromethyl)benzoic acid (80 mg) and HATU (129 mg). The reaction was stirred at RT for 14 h, diluted with water, filtered, and purified by RP-HPLC to afford 1-{2-[((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl]-4-(trifluoromethyl)phenyl}-3-ethylurea. MS found: (M+H)+=554.4. [Note: for larger scale preparations, the reaction was frequently run with CH2Cl2 as a co-solvent, and the following aqueous workup was used before RP-HPLC purification. Volatiles were removed and the residue was dissolved in EtOAc. The organic phase was washed with sat. NaHCO3, water, 1N HCl, sat. NaCl, and then dried (MgSO4), filtered, and concentrated in vacuo.]

Workup

  1. filtrationfiltered
  2. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-d02653c4abc84c21a2fd6441b1d1b301
Source dataset
uspto-grants-2007_01
Patent number
US07163937B2

Reaction notes

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