N-methyl-2-pyrrolidone → N-[4-(1-{1-(4-Chlorophenyl)-2-[5-(2-methoxypyridin-3-yl)-1,3-dihydro-2H-isoindol-2-yl]-2-oxoethyl}butyl)benzoyl]-beta-alanine

HRID 2190892Notes

Reaction equation

HRID 2190892 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:12]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([NH:24][CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])=[O:23])=[CH:18][CH:17]=2)[CH2:13][CH2:14][CH3:15])[C:9](O)=[O:10])=[CH:4][CH:3]=1.CN(C(ON1N=N[C:42]2[CH:43]=[CH:44][CH:45]=[N:46][C:41]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Br[C:66]1[CH:67]=[C:68]2[C:72](=[CH:73][CH:74]=1)[CH2:71][NH:70][CH2:69]2.CN1[C:80](=[O:81])CCC1>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH:12]([C:16]2[CH:17]=[CH:18][C:19]([C:22]([NH:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[O:23])=[CH:20][CH:21]=2)[CH2:13][CH2:14][CH3:15])[C:9]([N:70]2[CH2:71][C:72]3[C:68](=[CH:67][CH:66]=[C:74]([C:42]4[C:41]([O:81][CH3:80])=[N:46][CH:45]=[CH:44][CH:43]=4)[CH:73]=3)[CH2:69]2)=[O:10])=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 147958715-BromoisoindolineHCID 585538202-(4-Chlorophenyl)-3-(4-{[(3-ethoxy-3-oxopropyl)amino]carbonyl}phenyl)hexanoic acid

Product 1

HCID 46870236N-[4-(1-{1-(4-Chlorophenyl)-2-[5-(2-methoxypyridin-3-yl)-1,3-dihydro-2H-isoindol-2-yl]-2-oxoethyl}butyl)benzoyl]-beta-alanine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of a single stereoisomer (of the four possible) of 2-(4-chlorophenyl)-3-(4-{[(3-ethoxy-3-oxopropyl)amino]carbonyl}phenyl)hexanoic acid (EXAMPLE 1, Step C, 142 mg, 0.318 mmol) in NMP (3 mL) at room temperature was added HATU (133 mg, 0.350 mmol) and DIPEA (222 μl, 1.27 mmol). After one hour, 5-bromoisoindoline (94 mg, 0.48 mmol) was added, then the mixture was stirred at rt until the reaction was complete by LC-MS analysis. The mixture was then diluted with EtOAc then washed with water then saturated NaCl (aq). The organic layer was then dried over Na2SO4, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to provide the title compound as a white solid. LC2 1.53 min. (M+H)+ 627.

Workup

  1. washthen washed with water
  2. dry with materialThe organic layer was then dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by silica gel chromatography
  6. washeluting with 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-7fec6bb96cfd48bcb8c265596c12114b
Source dataset
uspto-grants-2012_12
Patent number
US08324384B2

Reaction notes

Loading…