Diisopropylethylamine → tert-Butyl 3-{3-[(4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoyl)amino]phenyl}propanoate

HRID 877258Notes

Reaction equation

HRID 877258 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:5]=[CH:6][CH:7]=1.[F:17][C:18]([F:44])([F:43])[CH:19]([CH3:42])[CH:20]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30][N:31]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][C:37]=3[F:40])[C:32]2=[O:41])=[CH:26][CH:25]=1)[C:21](O)=[O:22].O.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:44][C:18]([F:17])([F:43])[CH:19]([CH3:42])[CH:20]([C:24]1[CH:25]=[CH:26][C:27]([CH2:30][N:31]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][C:37]=3[F:40])[C:32]2=[O:41])=[CH:28][CH:29]=1)[C:21]([NH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:5]=[CH:6][CH:7]=1)=[O:22]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16731538tert-Butyl 3-(3-aminophenyl)propanoateHCID 581367454,4,4-Trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid

Product 1

HCID 58136487tert-Butyl 3-{3-[(4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoyl)amino]phenyl}propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

215.3 mg (0.89 mmol) of tert-butyl 3-(3-aminophenyl)propanoate were added to a solution of 280.0 mg (0.71 mmol) of 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid and 114.8 mg (0.85 mmol) of 1-hydroxy-1H-benzotriazole hydrate in 1.4 ml of DMF. At 0° C., 308 μl (1.77 mmol) of DIEA and then, a little at a time, 296.2 mg (0.78 mmol) of HATU were added to the resulting mixture. The reaction mixture was then slowly warmed to RT and subsequently stirred at RT for 2.5 h. The mixture was added to water and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 333 mg (78.6% of theory) of the title compound.

Workup

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-ab530ac0c2f145d3825a835e38152ce9
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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