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

HRID 2196418Notes

Reaction equation

HRID 2196418 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][C:8]=1[F:16].Cl.[NH2:19][C@@H:20]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]([F:43])([F:42])[F:41])[CH2:21][N:22]1[C:30](=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:32].C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([NH:19][C@@H:20]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[C:40]([F:43])([F:41])[F:42])[CH2:21][N:22]2[C:30](=[O:31])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]2=[O:32])=[O:13])=[CH:9][C:8]=1[F:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 593549914-(4-chloro-1-methyl-1H-pyrazol-5-yl)-3-fluorobenzoic acidHCID 670654562-{(2s)-2-Amino-3-[2-(trifluoromethyl)phenyl]propyl}-1h-isoindole-1,3(2h)-dione-hcl

Product 1

HCID 593550284-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-3-fluorobenzamideYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-3-fluorobenzoic acid (100 mg, 0.43 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione-HCl (151 mg, 0.43 mmol) [prepared according to Preparation 3], diisopropylethyl amine (0.4 mL, 2.14 mmol) in DCM (5 mL) was added PyBrop (330 mg, 0.71 mmol) in one portion. After 1 h, the reaction contents were partitioned between H2O/DCM. The aqueous phase was washed several times with DCM. The combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica) affording the title compound (90 mg, 36%) as a white solid: LCMS (ES) m/z=585 (M+H)+.

Workup

  1. customthe reaction contents
  2. customwere partitioned between H2O/DCM
  3. washThe aqueous phase was washed several times with DCM
  4. dry with materialThe combined organic fractions were dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified via column chromatography (silica)

Sources & evidence

ORD record
ord-63d7af49c5404fce82dfc064bd4f1665
Source dataset
uspto-grants-2012_12
Patent number
US08338434B2

Reaction notes

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