Diisopropylamine → {2-[3-Chloro-5-(diisopropylcarbamoyl)-phenoxy]-ethyl}-pyridin-4-yl-carbamic acid tert-butyl ester

HRID 2268617Notes

Reaction equation

HRID 2268617 reaction equation
[C:1]([O:5][C:6]([N:8]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)[CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([Cl:21])[CH:20]=1)[C:15](O)=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.CC[N:36]([CH:40]([CH3:42])[CH3:41])[CH:37]([CH3:39])[CH3:38].C(NC(C)C)(C)C>O1CCCC1.CN(C1C=CN=CC=1)C.CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([C:15](=[O:16])[N:36]([CH:40]([CH3:42])[CH3:41])[CH:37]([CH3:39])[CH3:38])[CH:18]=[C:19]([Cl:21])[CH:20]=1)[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 18348849Benzoic acid,3-chloro-5-[2-[[(1,1-dimethylethoxy)carbonyl]-4-pyridinylamino]ethoxy]-

Product 1

HCID 53659675{2-[3-Chloro-5-(diisopropylcarbamoyl)-phenoxy]-ethyl}-pyridin-4-yl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.10 g) in tetrahydrofuran (5 ml) was added DMF (0.005 ml) and oxalyl chloride (0.175 ml). After 0.5 h DIPEA (0.13 ml), diisopropylamine (0.20 ml) and DMAP (0.002 g) were added. After 18 h the mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The combined organic phases were washed with brine and dried over magnesium sulphate. Filtration and evaporation gave the crude product which was purified by flash column chromatography on silica eluting with cyclohexane/ethyl acetate (1:3). This afforded the title compound as a colourless gum (0.078 g).

Workup

  1. customAfter 18 h the mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over magnesium sulphate
  4. filtrationFiltration and evaporation
  5. customgave the crude product which
  6. customwas purified by flash column chromatography on silica eluting with cyclohexane/ethyl acetate (1:3)

Sources & evidence

ORD record
ord-554232938e2d465d871f51832e6dd5f1
Source dataset
uspto-grants-2001_12
Patent number
US06326386B1

Reaction notes

Loading…