Diisopropylethylamine → (R)-2-cyclohexylmethyl-N-[2-(4-fluoro-phenylamino)-ethyl]-succinamic acid methyl ester

HRID 1783858Notes

Reaction equation

HRID 1783858 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)[CH2:5][C:6]([OH:8])=O.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:50][C:51]1[CH:56]=[CH:55][C:54]([NH:57][CH2:58][CH2:59][NH2:60])=[CH:53][CH:52]=1>ClCCl>[CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)[CH2:5][C:6]([NH:60][CH2:59][CH2:58][NH:57][C:54]1[CH:55]=[CH:56][C:51]([F:50])=[CH:52][CH:53]=1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2734511(R)-2-(Cyclohexylmethyl)succinic acid-1-methyl esterHCID 3016534N-(4-Fluorophenyl)ethylenediamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 68481422(R)-2-cyclohexylmethyl-N-[2-(4-fluoro-phenylamino)-ethyl]-succinamic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-2-(Cyclohexylmethyl)succinic acid-1-methyl ester (211 mg, 0.93 mmol) from Acros Organics was treated with (500 μL, 2.87 mmol, 3.1 eq.) of diisopropylethylamine, HATU (360 mg, 1.096 mmol, 1.2 eq.) and (N-(4-Fluoro-phenyl)-ethane-1,2-diamine) (210 mg, 0.93 mmol, 1 eq.). The reagents were dissolved in dry dichloromethane (5 mL). The reaction was allowed to stir for 5 hours and monitored by LC/MS. Volatiles were removed and the reaction directly purified by automated normal-phase chromatography (0-100% ethyl acetate in hexanes gradient). (R)-2-cyclohexylmethyl-N-[2-(4-fluoro-phenylamino)-ethyl]-succinamic acid methyl ester was obtained as clear oil (220 mg, 0.60 mmol, 65%).

Workup

  1. customVolatiles were removed
  2. customthe reaction
  3. customdirectly purified by automated normal-phase chromatography (0-100% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-f869eb9b164c4cca94362b68c0e38e8d
Source dataset
uspto-grants-2009_03
Patent number
US07501408B2

Reaction notes

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