1,2-Dichloroethane → N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-[4-(5-methylisoxazol-4-yl)phenyl]acetamide

HRID 254692Notes

Reaction equation

HRID 254692 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[CH:4][C:3]=1[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([OH:16])=O)=[CH:9][CH:8]=1.Cl.[Br:18][C:19]1[CH:20]=[CH:21][C:22]([C@H:25]([NH2:27])[CH3:26])=[N:23][CH:24]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([C@H:25]([NH:27][C:14](=[O:16])[CH2:13][C:10]2[CH:9]=[CH:8][C:7]([C:3]3[CH:4]=[N:5][O:6][C:2]=3[CH3:1])=[CH:12][CH:11]=2)[CH3:26])=[N:23][CH:24]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 50999177(R)-1-(5-Bromopyridin-2-yl)ethanamine hydrochlorideHCID 66893040[4-(5-Methylisoxazol-4-yl)phenyl]acetic acid

Product 1

HCID 24765670N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-[4-(5-methylisoxazol-4-yl)phenyl]acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.20 g (0.921 mmol) [4-(5-methylisoxazol-4-yl)phenyl]acetic acid in 2.00 ml DMF was added 0.22 g (0.92 mmol) (1R)-1-(5-bromopyridin-2-yl)ethanamine hydrochloride salt, 0.16 g (1.20 mmol) HOAT, 0.23 g (1.20 mmol) EDC, and 0.48 mL (2.76 mmol) DIEA. After 1.5 h at room temperature, the reaction mixture was diluted with CH2Cl2, washed three times with water, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (1×14 cm silica gel, linear gradient 38-85% EtOAc:hexane) afforded N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-[4-(5-methylisoxazol-4-yl)phenyl]acetamide. 1H NMR (CDCl3, 400 MHz) 8.53 (d, 1H, J=2.11 Hz); 8.35 (s, 1H); 7.76 (dd, 1H, J=2.38 Hz, 8.33 Hz); 7.35 (s, 4H); 7.13 (d, 1H, J=8.24 Hz); 6.73 (br d, 1H, J=6.32 Hz); 5.11 (m, 1H); 3.61 (s, 2H); 2.58 (s, 3H); 1.42 (d, 3H, J=6.87). Electrospray mass spec M+H=402.0.

Workup

  1. washwashed three times with water
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (1×14 cm silica gel, linear gradient 38-85% EtOAc:hexane)

Sources & evidence

ORD record
ord-63d1d1a0a7184384a0bb1e618689913d
Source dataset
uspto-grants-2011_01
Patent number
US07875636B2

Reaction notes

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