Diisopropylethylamine → benzyl 2-(5-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate

HRID 515391Notes

Reaction equation

HRID 515391 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]3[CH2:19][O:18][CH:17]([CH2:20][C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])[CH2:16][CH2:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:31][C:32]1[O:33][C:34]([C:40]([F:43])([F:42])[F:41])=[C:35]([C:37](O)=[O:38])[N:36]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:31][C:32]1[O:33][C:34]([C:40]([F:43])([F:41])[F:42])=[C:35]([C:37]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:9]=[CH:10][C:11]([CH:14]4[CH2:19][O:18][CH:17]([CH2:20][C:21]([O:23][CH2:24][C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)=[O:22])[CH2:16][CH2:15]4)=[CH:12][CH:13]=3)=[CH:4][CH:3]=2)=[O:38])[N:36]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27756512-methyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89872737benzyl 2-(5-(4'-amino-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate

Product 1

HCID 89872728benzyl 2-(5-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetateYield 81.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of benzyl 2-(5-(4′-amino-[1,1′-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate (118 mg, 0.294 mmol) in DMF (2 ml) at room temperature was added 2-methyl-5-(trifluoromethyl)oxazole-4-carboxylic acid (74.5 mg, 0.382 mmol) and DIPEA (0.103 ml, 0.588 mmol) and the reaction was stirred at room temperature for 10 min then was added HATU (145 mg, 0.382 mmol). The reaction was stirred at room temperature for 30 min. The reaction was quenched by brine and was extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (10 to 50% EtOAc/Heptane) to give the title compound 138 mg (yield 81%). MS (ESI) m/z 579.4 (M+1). Retention time 1.69 min (condition A).

Workup

  1. stirringThe reaction was stirred at room temperature for 30 min
  2. customThe reaction was quenched by brine
  3. extractionwas extracted with EtOAc
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (10 to 50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-812cb9a344b54bafa33bb1a21351a731
Source dataset
uspto-grants-2015_08
Patent number
US09108956B2

Reaction notes

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