1,2-Dichloroethane → (S)-ethyl 5-amino-6-(4-((1-(3-bromo-5-fluorophenyl)-2-hydroxyethyl)carbamoyl)-3-fluorophenyl)pyrazine-2-carboxylate

HRID 596126Notes

Reaction equation

HRID 596126 reaction equation
[NH2:1][C:2]1[C:3]([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[C:15]([F:22])[CH:14]=2)=[N:4][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:7]=1.[NH2:23][C@@H:24]([C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([Br:34])[CH:28]=1)[CH2:25][OH:26].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:4][C:3]=1[C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:19])[NH:23][C@@H:24]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([Br:34])[CH:28]=2)[CH2:25][OH:26])=[C:15]([F:22])[CH:14]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 66514746(S)-2-Amino-2-(3-bromo-5-fluorophenyl)ethan-1-OLHCID 1180454784-(3-Amino-6-(ethoxycarbonyl)pyrazin-2-yl)-2-fluorobenzoic acid

Product 1

HCID 118054716(S)-ethyl 5-amino-6-(4-((1-(3-bromo-5-fluorophenyl)-2-hydroxyethyl)carbamoyl)-3-fluorophenyl)pyrazine-2-carboxylateYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 4-(3-amino-6-(ethoxycarbonyl)pyrazin-2-yl)-2-fluorobenzoic acid (0.214 g, 0.7 mmol), (S)-2-amino-2-(3-bromo-5-fluorophenyl)ethanol (272 mg, 1.009 mmol),HOAt (187 mg, 1.376 mmol) and EDC (264 mg, 1.376 mmol) in DMF (2.5 mL) was added DIEA (0.961 mL, 5.50 mmol). The resultant mixture was stirred over night at RT. The mixture was diluted with EtOAc, washed with water three times and brine, dried, concentrated to afford the crude product as a light yellow viscous liquid. ISCO purification (12 g silica, 10 to 90% EtOAc in heptane, 30 min) provided the desired product (200 mg, 84% yield) as a light yellow liquid. LC-MS (m/z): 522.9 (MH+), 0.787 min.

Workup

  1. washwashed with water three times and brine
  2. customdried
  3. concentrationconcentrated
  4. customto afford the crude product as a light yellow viscous liquid
  5. customISCO purification (12 g silica, 10 to 90% EtOAc in heptane, 30 min)

Sources & evidence

ORD record
ord-854a6210acb24d218e83fda098d149fe
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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