Ethylmorpholine → HCID 66628443, compound

HRID 240254Notes

Reaction equation

HRID 240254 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:12]([C:17]([O:19][CH3:20])=[O:18])[C:13]([O:15][CH3:16])=[O:14])[C:9]#[C:10][CH3:11])=[CH:4][CH:3]=1.C([N:23]1CCOCC1)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.[Br:51][C:52]1[CH:64]=[CH:63][C:55]([O:56][C:57]([CH3:62])([CH3:61])[C:58](O)=[O:59])=[C:54]([Cl:65])[CH:53]=1>CN(C=O)C>[Br:51][C:52]1[CH:64]=[CH:63][C:55]([O:56][C:57]([CH3:62])([CH3:61])[C:58]([NH:23][C:6]2[CH:7]=[CH:2][CH:3]=[CH:4][C:5]=2[CH:8]([CH:12]([C:17]([O:19][CH3:20])=[O:18])[C:13]([O:15][CH3:16])=[O:14])[C:9]#[C:10][CH3:11])=[O:59])=[C:54]([Cl:65])[CH:53]=1

Participants

7

Reactant 5

HCID 7525Ethylmorpholine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrate2×HCID 50079112-(4-bromo-2-chlorophenoxy)-2-methylpropanoic acidHCID 59132632HCID 59132632, compound

Product 1

HCID 66628443HCID 66628443, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 200 mg (0.73 mmol) of dimethyl 2-[1-(4-aminophenyl)but-2-ynyl]-malonate, 251 mg (2.18 mmol) of N-ethylmorpholine, 122 mg (0.8 mmol) of HOBt hydrate and 124 mg (0.80 mmol) of EDAC in 5 ml of DMF was added a solution of 213 mg (0.73 mmol) of 2-(4-bromo-2-chlorophenoxy)-2-methylpropionic acid in 3 ml of DMF. After 18 h at room temperature, another 1.1 equivalents each of N-ethylmorpholine and HOBt hydrate were added. After 72 h, the reaction mixture was concentrated completely and separated by means of preparative HPLC (Merck Hibar Purospher Star RP-18e 10 μm 25×250 mm; A: H2O+0.05% TFA; B: ACN+0.05% TFA; flow rate: 50 ml/min; in 10 minutes 10% B→80% B; in 5 minutes 80% B→90% B). The product fractions were freeze-dried to obtain 180 mg (45%) of dimethyl 2-(1-{-[2-(4-bromo-2-chlorophenoxy)-2-methylpropionylamino]phenyl}but-2-ynyl)malonate.

Workup

  1. waitAfter 72 h
  2. concentrationthe reaction mixture was concentrated completely
  3. customseparated by means of preparative HPLC (Merck Hibar Purospher Star RP-18e 10 μm 25×250 mm
  4. waitin 10 minutes 10% B→80% B
  5. waitin 5 minutes 80% B→90% B)
  6. customThe product fractions were freeze-dried

Sources & evidence

ORD record
ord-a2e387d9df6648679319f4edc05a08e2
Source dataset
uspto-grants-2014_02
Patent number
US08648038B2

Reaction notes

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