Diisopropylethylamine → 4-bromo-5-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide

HRID 2391983Notes

Reaction equation

HRID 2391983 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([OH:10])=O)[S:5][C:6]=1[Cl:7].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:44][C@@H:45]([CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=1[C:65]([F:68])([F:67])[F:66])[CH2:46][N:47]1[C:55](=[O:56])[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[C:48]1=[O:57]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([NH:44][C@@H:45]([CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[C:65]([F:68])([F:66])[F:67])[CH2:46][N:47]2[C:55](=[O:56])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[C:48]2=[O:57])=[O:10])[S:5][C:6]=1[Cl:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 148824034-Bromo-5-chlorothiophene-2-carboxylic acidHCID 578268082-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione

Product 1

HCID 578266774-bromo-5-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-bromo-5-chloro-2-thiophenecarboxylic acid (1.3 g, 5.42 mmol), PyBrOP (3 g, 6.5 mmol) and diisopropylethyl amine (4.7 mL, 27.1 mmol) in DCM (54 mL) at 25° C. was added 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (2.0 g, 5.42 mmol)[prepared in Preparation 6]. After 1 h, the solution was partitioned between H2O and washed with DCM. The combined organic fractions were dried (Na2SO4), concentrated and used directly: LCMS (ES) m/z=572 (M+H)+.

Workup

  1. customthe solution was partitioned between H2O
  2. washwashed with DCM
  3. dry with materialThe combined organic fractions were dried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-d5298b632e0b4d80855ad03ee07af942
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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