Acetonitrile → (S)-2-Amino-3-(4-(5-(biphenyl-4-ylmethylamino)pyrazin-2-yl)phenyl)propanoic acid

HRID 469872Notes

Reaction equation

HRID 469872 reaction equation
[C:1]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[CH:5][C:4]([CH2:7][NH:8][C:9]2[CH:14]=[N:13][C:12](Br)=[CH:11][N:10]=2)=[CH:3][CH:2]=1.[C:22]([O-:25])([O-])=[O:23].[Na+].[Na+].[C:28](#[N:30])[CH3:29]>[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd+2].O>[NH2:30][C@@H:28]([CH2:29][C:1]1[CH:6]=[CH:5][C:4]([C:12]2[CH:11]=[N:10][C:9]([NH:8][CH2:7][C:4]3[CH:5]=[CH:6][C:1]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:2][CH:3]=3)=[CH:14][N:13]=2)=[CH:3][CH:2]=1)[C:22]([OH:25])=[O:23]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 86614306N-(biphenyl-4-ylmethyl)-5-bromopyrazin-2-amine

Product 1

HCID 24894612(S)-2-Amino-3-(4-(5-(biphenyl-4-ylmethylamino)pyrazin-2-yl)phenyl)propanoic acid

Reagents, catalysts & solvents 2

HCID 22065850Palladium(2+);triphenylphosphane;dichlorideCatalystHCID 962WaterSolvent

Procedure

N-(biphenyl-4-ylmethyl)-5-bromopyrazin-2-amine (60 mg, 0.176 mmol), L-p-boronophenylalanine (37 mg, 0.176 mmol), palladiumtriphenylphosphine dichloride (3.6 mg, 0.0052 mmol), Na2CO3 (37 mg, 0.353 mmol), acetonitrile (1.25 mls) and water (1.25 mls) were heated in a microwave reactor at 150° C. for 5 minutes. The mixture was concentrated, dissolved in 1.0 N HCl, washed twice with ether, concentrated and purified by preprative HPLC to give 41 mgs of the title compound. M+1=425; 1H NMR (CD3OD) δ 8.42 (s, 1H), 8.05 (s, 1H), 7.92 (d, 2H), 7.58 (d, 4H), 7.40 (m, 7H), 4.60 (s, 2H), 4.25 (m, 1H), 3.40 (m, 1H), 3.20 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in 1.0 N HCl
  3. washwashed twice with ether
  4. concentrationconcentrated
  5. custompurified by preprative HPLC

Sources & evidence

ORD record
ord-dc2d4ccc0ad249bd8450c21a4bfea09a
Source dataset
uspto-grants-2014_01
Patent number
US08629156B2

Reaction notes

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