1,2-Dichloroethane → (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide

HRID 596011Notes

Reaction equation

HRID 596011 reaction equation
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[N:24]([CH2:27][C@H:28]([C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([Cl:37])[CH:31]=1)[NH2:29])=[N+:25]=[N-:26].CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:29][C@@H:28]([C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([Cl:37])[CH:31]=3)[CH2:27][N:24]=[N+:25]=[N-:26])=[O:19])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 1180447134-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118046055(S)-2-azido-1-(3-chloro-5-fluorophenyl)ethanamine

Product 1

HCID 118046045(S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamideYield 58%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (126 mg, 0.398 mmol) in DMF (1328 μl) was added (S)-2-azido-1-(3-chloro-5-fluorophenyl)ethanamine (100.0 mg, 0.398 mmol), DIEA (348 μl, 1.991 mmol), EDC (153 mg, 0.797 mmol), and aza-HOBt (81 mg, 0.597 mmol). The reaction mixture was stirred for 15 h. After water was added, the reaction mixture was worked up with EtOAc. The organic layer was dried over Na2SO4, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography (gradient EtOAc in heptane) to provide (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 58%). LCMS (m/z): 514.2 (MH+), 0.91 min.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered off
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography (gradient EtOAc in heptane)

Sources & evidence

ORD record
ord-55f3fedf4c7143c69d924429aeebafb1
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

Loading…