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

HRID 1961186Notes

Reaction equation

HRID 1961186 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:12]([OH:14])=O)[S:10][CH:11]=2)=[CH:5][CH:4]=[N:3]1.[NH2:15][C@@H:16]([CH2:29][C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1[F:37])[CH2:17][N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:28].FC1C=CC=C(F)C=1C[C@@H](C(O)=O)N.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[F:37][C:31]1[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:30]=1[CH2:29][C@H:16]([NH:15][C:12]([C:9]1[S:10][CH:11]=[C:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=2)[CH:8]=1)=[O:14])[CH2:17][N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:28]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 7163042,6-Difluoro-l-phenylalanineHCID 2733179PyBroPHCID 578264554-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic AcidHCID 670660702-[(2S)-2-amino-3-(2,5-difluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 57826382N-{(1S)-2-(2,5-difluorophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamideYield 54.8%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a 50 mL round-bottomed flask was added 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (257 mg, 0.93 mmol) [prepared according to the procedure of Example 146], 2-[(2S)-2-amino-3-(2,5-difluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (476 mg, 0.81 mmol) [prepared according to the procedure of Preparation 18 except substituting 2,5-difluoro-L-phenylalanine (3.02 g, 15.0 mmol) for 2,6-difluoro-L-phenylalanine] and PyBrop (535 mg, 1.14 mmol) in Chloroform (15 mL). DIEA (0.808 mL, 4.63 mmol) was added and the reaction stirred overnight at room temperature. The mixture was adsorbed onto silica and purified via column chromatography (25-75% EtOAc/Hex) affording the title compound (225 mg, 34%): LC-MS (ES) m/z=507 (M+H)+

Workup

  1. customprepared
  2. customprepared
  3. customaccording to the procedure of Preparation 18
  4. custompurified via column chromatography (25-75% EtOAc/Hex)

Sources & evidence

ORD record
ord-73e412d9175748b7915d914f78d6b876
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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