3-Aminopyridine → HCID 54596225, compound

HRID 1853144Notes

Reaction equation

HRID 1853144 reaction equation
Br[C:2]1[N:3]=[C:4]([C:16](=[O:31])[N:17](C(OC(C)(C)C)=O)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]([NH:8]C(=O)OC(C)(C)C)=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[N:38]1[CH:43]=[CH:42][CH:41]=[C:40]([NH2:44])[CH:39]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C1(C=CC(=O)C=CC2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.[Pd]>[NH2:8][C:5]1[C:4]([C:16]([NH:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:31])=[N:3][C:2]([NH:44][C:40]2[CH:39]=[N:38][CH:43]=[CH:42][CH:41]=2)=[CH:7][N:6]=1

Participants

8

Reactant 5

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 95417Dibenzylidene acetoneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 58084321HCID 58084321, compound

Product 1

HCID 54596225HCID 54596225, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 1140TolueneSolvent

Procedure

tert-Butyl N-[5-bromo-3-[tert-butoxycarbonyl(phenyl)carbamoyl]pyrazin-2-yl]carbamate (60 mg, 0.1216 mmol), dicesium carbonate (118.9 mg, 0.3648 mmol), pyridin-3-amine (17.17 mg, 0.1824 mmol), 2-(2-dicyclohexylphosphanylphenyl)-N,N-dimethyl-aniline (14.36 mg, 0.03648 mmol), 1,5-diphenylpenta-1,4-dien-3-one; palladium (11.14 mg, 0.01216 mmol) in toluene (06. mL) heated under microwave conditions at 130° C. for 30 minutes. The reaction mixture was filtered and the filtrate diluted with DCM (2 mL) and TFA (0.5 mL) was added. The resulting solution was stirred at ambient temperature for 30 minutes then concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as an yellow solid (7 mg, 19% Yield). 1H NMR (400.0 MHz, DMSO) δ 9.99 (s, 1H), 9.86 (s, 1H), 9.12 (s, 1H), 8.30 (d, J=4.8 Hz, 1H), 8.20 (d, J=3.4 Hz, 2H), 7.75 (dd, J=7.7, 16.7 Hz, 3H), 7.41-7.37 (m, 2H), 7.22 (s, 1H) and 7.14 (t, J=7.4 Hz, 2H) ppm; MS (ES+) 307.

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionthe filtrate diluted with DCM (2 mL) and TFA (0.5 mL)
  3. additionwas added
  4. concentrationthen concentrated in vacuo
  5. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  6. customThe fractions were collected
  7. customfreeze-dried

Sources & evidence

ORD record
ord-6537b4d92a8540e0aecc51e9ade0bb37
Source dataset
uspto-grants-2015_02
Patent number
US08962631B2

Reaction notes

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