Diisopropylethylamine → 4-(Methoxymethyl)-4'-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenyl

HRID 1519670Notes

Reaction equation

HRID 1519670 reaction equation
Cl.[CH3:2][NH:3][C:4](=[O:12])[C@H:5]([C:8](=[O:11])[O:9][CH3:10])[NH:6][CH3:7].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:46][O:47][CH2:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]2[CH:60]=[CH:59][C:58]([C:61]([OH:63])=O)=[CH:57][CH:56]=2)=[CH:51][CH:50]=1>[Cl-].[Na+].O.CN(C=O)C>[CH3:46][O:47][CH2:48][C:49]1[CH:50]=[CH:51][C:52]([C:55]2[CH:56]=[CH:57][C:58]([C:61](=[O:63])[N:6]([CH:5]([C:4]([NH:3][CH3:2])=[O:12])[C:8]([O:9][CH3:10])=[O:11])[CH3:7])=[CH:59][CH:60]=2)=[CH:53][CH:54]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712682094'-(Methoxymethyl)biphenyl-4-carboxylic acidHCID 86679246N,N2,O-trimethyl-3-oxoserinamide hydrochloride

Product 1

HCID 712681484-(Methoxymethyl)-4'-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenylYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

Intermediate 5-2 (0.39 g), HATU (0.57 g) and DIPEA (0.80 mL) were added to a DMF (6.0 mL) solution of 4′-(methoxymethyl)biphenyl-4-carboxylic acid (0.36 g) as obtained in Example 3-(3), and the mixture was stirred for 30 minutes at 80° C. Then, brine was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The desiccant was filtered out, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by NH type silica gel chromatography (gradient elution with hexane/ethyl acetate=50/50→0/100) to obtain 4-(methoxymethyl)-4′-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenyl (yellow oil) (0.40 g, 69%).

Workup

  1. customas obtained in Example 3-(3)
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationThe desiccant was filtered out
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by NH type silica gel chromatography (gradient elution with hexane/ethyl acetate=50/50→0/100)

Sources & evidence

ORD record
ord-c3caa28f1c3a4b93a75f9ba6fdb9196d
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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