Diisopropylethylamine → tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate

HRID 1026221Notes

Reaction equation

HRID 1026221 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:22])[CH2:10][O:11][C:12]1[CH:13]=[C:14]([F:21])[C:15]([C:18]([OH:20])=O)=[N:16][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][C:26]=1[OH:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O.CN(C=O)C>[OH:32][C:26]1[CH:27]=[C:28]([OH:31])[CH:29]=[CH:30][C:25]=1[NH:24][C:18]([C:15]1[N:16]=[CH:17][C:12]([O:11][CH2:10][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:22])=[CH:13][C:14]=1[F:21])=[O:20]

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 134088224-Aminobenzene-1,3-diol hydrochlorideHCID 677781795-({(2S)-2-[(tert-butoxycarbonyl)amino]propyl}oxy)-3-fluoropyridine-2-carboxylic acid

Product 1

HCID 86666268tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamateYield 67.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-({(2S)-2-[(tert-butoxycarbonyl)amino]propyl}oxy)-3-fluoropyridine-2-carboxylic acid (357 mg), 4-aminobenzene-1,3-diol hydrochloride (184 mg), HATU (432 mg), N,N-diisopropylethylamine (0.391 mL) and DMF (5 mL) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (321 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-af298bcc0d564afd93bf4c329844d755
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

Loading…