Nitrogen → 4-(5-Amino-6-(phenylcarbamoyl)pyrazin-2-yl)benzoic acid

HRID 78578Notes

Reaction equation

HRID 78578 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.B([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)(O)O.C([O-])([O-])=O.[Na+].[Na+].N#N>CC#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:21]2[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=2)=[N:4][C:3]=1[C:9](=[O:10])[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 529371483-amino-6-bromo-N-phenylpyrazine-2-carboxamide

Product 1

HCID 468337444-(5-Amino-6-(phenylcarbamoyl)pyrazin-2-yl)benzoic acidYield 73.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-amino-6-bromo-N-phenyl-pyrazine-2-carboxamide (3.62 g, 12.35 mmol), 4-boronobenzoic acid (2.049 g, 12.35 mmol) and Na2CO3 (2.618 g, 24.70 mmol) was suspended in MeCN (60 mL)/water (60 mL). The mixture was degassed (5×N2 vacuum cycles) and Pd(PPh3)4 (1.427 g, 1.235 mmol) added. The mixture was degassed again and heated to 90° C. After 4 hours, the mixture was allowed to cool, concentrated to half its original volume and washed with DCM. The aqueous phase was acidified to pH4 (2M HCl) and the resulting precipitate collected, washed with water and dried overnight under vacuum to give the product as a bright yellow solid, (3.05 g, 69% Yield). 1H NMR (400 MHz, DMSO) d 7.17 (1H, t), 7.41 (2H, t), 7.83 (4H, d), 8.03 (2H, d), 8.37 (2H, d), 9.01 (1H, s), 10.45 (1H, s), 13.03 (1H, brs) ppm; MS (ES+) 335

Workup

  1. additionadded
  2. customThe mixture was degassed again
  3. temperatureto cool
  4. concentrationconcentrated to half its original volume
  5. washwashed with DCM
  6. customthe resulting precipitate collected
  7. washwashed with water
  8. customdried overnight under vacuum

Sources & evidence

ORD record
ord-f6acd6bfa6474a2ca2a016ace68f4a3f
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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