Potassium Phosphate, Tribasic → HCID 86698331, compound

HRID 1497845Notes

Reaction equation

HRID 1497845 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][CH2:10][CH2:11][N:12]([CH3:14])[CH3:13])[CH:5]=[C:6]([F:8])[CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:47]1[CH:48]=[N:49][CH:50]=[C:51]([N+:54]([O-:56])=[O:55])[C:52]=1[NH2:53]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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.CN(C=O)C>[NH2:53][C:52]1[C:51]([N+:54]([O-:56])=[O:55])=[CH:50][N:49]=[CH:48][C:47]=1[C:2]1[CH:3]=[C:4]([NH:9][CH2:10][CH2:11][N:12]([CH3:14])[CH3:13])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

10

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 49975884-Amino-3-bromo-5-nitropyridineHCID 86698330HCID 86698330, compound

Product 1

HCID 86698331HCID 86698331, compoundYield 54%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of N1-(3-bromo-5-fluorophenyl)-N2,N2-dimethylethane-1,2-diamine (LXXV) (5 g, 19.15 mmol), bis(pinacolato)diboron (5.83 g, 22.98 mmol), KOAc (5.63 g, 57.45 mmol) and dry DMF (20 mL) was purged with argon. PdCl2(dppf)2 (938 mg, 1.15 mmol) was added to the reaction and purged again with argon. The solution was heated at 95° C. for 2 h. Once TLC showed the disappearance of (LXXV), the solution was cooled to room temperature. To this solution was added K3PO4 (6.09 g, 28.72 mmol), 3-bromo-5-nitropyridin-4-amine (LVIII) (4.17 g, 19.15 mmol), Pd(PPh3)4 (663 mg, 0.57 mmol) and water (4 mL). The solution was purged with argon and heated at 100° C. for 4 h. The solution was cooled to room temperature and then concentrated under reduced pressure. The residue was partitioned between DCM and water. The aqueous phase was filtered through Celite® and concentrated under vacuum. The residue was purified on a silica gel column (100% CHCl3→5:95 MeOH:CHCl3) to give N1-(3-(4-amino-5-nitropyridin-3-yl)-5-fluorophenyl)-N2,N2-dimethylethane-1,2-diamine (LXXVII) as a yellow amorphous solid (3.30 g, 10.33 mmol, 54.0% yield for 2 steps). 1H NMR (DMSO-d6, 500 MHz) δ ppm 2.18 (s, 6H), 2.44 (t, J=6.5 Hz, 2H), 3.12 (q, J=6 Hz, 2H), 6.01 (t, J=5 Hz, 1H), 6.35 (d, J=9 Hz, 1H), 6.43 (s, 1H), 6.48 (dt, J=10 Hz, J=2 Hz, 1H), 7.32 (brs, 2H), 8.10 (s, 1H), 9.01 (s, 1H); ESIMS found for C15H18FN5O2 m/z 320.3 (M+H).

Workup

  1. custompurged again with argon
  2. temperaturethe solution was cooled to room temperature
  3. customThe solution was purged with argon
  4. temperatureheated at 100° C. for 4 h
  5. temperatureThe solution was cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was partitioned between DCM and water
  8. filtrationThe aqueous phase was filtered through Celite®
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified on a silica gel column (100% CHCl3→5:95 MeOH:CHCl3)

Sources & evidence

ORD record
ord-eeb9d6ac268641b092d005a462dbb15d
Source dataset
uspto-grants-2015_12
Patent number
US09199991B2

Reaction notes

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