1,2-Dichloroethane → (S)-tert-butyl (2-(4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamido)-2-(3-bromo-5-fluorophenyl)ethyl)carbamate

HRID 596009Notes

Reaction equation

HRID 596009 reaction equation
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[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.[NH2:24][C@@H:25]([C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[C:37]([Br:42])[CH:36]=1)[CH2:26][NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:24][C@@H:25]([C:35]3[CH:40]=[C:39]([F:41])[CH:38]=[C:37]([Br:42])[CH:36]=3)[CH2:26][NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:20])=[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

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 1180447134-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118054648(S)-tert-butyl (2-amino-2-(3-bromo-5-fluorophenyl)ethyl)carbamate

Product 1

HCID 118054700(S)-tert-butyl (2-(4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamido)-2-(3-bromo-5-fluorophenyl)ethyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (35 mg, 0.110 mmol) in DMF (368 μl) was added (S)-tert-butyl (2-amino-2-(3-bromo-5-fluorophenyl)ethyl)carbamate (40.8 mg, 0.110 mmol), aza-HOBt (22.52 mg, 0.165 mmol). EDC (31.7 mg, 0.165 mmol), and DIEA (57.8 μl, 0.331 mmol). The reaction mixture was stirred at room temperature for 3 h, and then partitioned between EtOAc and water. The organic was washed by NaHCO3, water and brine, dried over Na2SO4 and concentrated. The crude (S)-tert-butyl (2-(4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamido)-2-(3-bromo-5-fluorophenyl)ethyl)carbamate was used in next step reaction without further purification. LCMS (m/z): 632.1/634.1 (MH+), 0.97 min.

Workup

  1. custompartitioned between EtOAc and water
  2. washThe organic was washed by NaHCO3, water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude (S)-tert-butyl (2-(4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzamido)-2-(3-bromo-5-fluorophenyl)ethyl)carbamate was used in next step reaction without further purification
  6. custom632.1/634.1 (MH+), 0.97 min.

Sources & evidence

ORD record
ord-8f693d56c97e414586fe578af9f60621
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

Loading…