Potassium Phosphate, Tribasic → HCID 58293789, compound

HRID 446737Notes

Reaction equation

HRID 446737 reaction equation
[C:1]([NH:5][C:6]1[C:11]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20](Br)=[C:19]([F:24])[C:18]=3[F:25])[N:15]=[N:14][N:13]=2)=[CH:10][CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].[CH:26]1([B-](F)(F)F)[CH2:28][CH2:27]1.[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.CC([O-])=O.CC([O-])=O.[Pd+2].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[C:1]([NH:5][C:6]1[C:11]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([CH:26]4[CH2:28][CH2:27]4)=[C:19]([F:24])[C:18]=3[F:25])[N:15]=[N:14][N:13]=2)=[CH:10][CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 23697338Potassium cyclopropyltrifluoroborateHCID 58293810HCID 58293810, compound2×

Product 1

HCID 58293789HCID 58293789, compoundYield 88.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
180 °C

Procedure

N-tert-Butyl-3-(1-(4-bromo-2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1080 150 mg, 0.366 mmol), potassium cyclopropyltrifluoroborate (70.5 mg, 0.476 mmol), tricyclohexylphosphine (10 mg, 0.0366 mmol) and K3PO4 (272 mg, 1.283 mmol) were taken into toluene (1.5 ml), and water (750 μL). The reaction was degassed with nitrogen for 1 hour and Pd(OAc)2 (4.1 mg, 0.0183 mmol) was added. The reaction mixture was heated at 180° C. for 10 minutes under microwave irradiation. The reaction was found to be incomplete by HPLC analysis so tetrakis-(triphenylphosphine) palladium (0) (42 mg, 0.0366 mmol) was added to the mixture and microwave irradiation was continued for 10 minutes at 180° C. The reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the volatiles removed under reduced pressure to afford a crude brown oil, which was purified by column chromatography (SiO2), eluting with 0-20% EtOAc/hexanes, to afford 120 mg of N-tert-butyl-3-(1-(4-cyclopropyl-2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1084) as a colorless oil; ESMS (M+1)=371.

Workup

  1. customThe reaction was degassed with nitrogen for 1 hour
  2. additionwas added to the mixture and microwave irradiation
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe volatiles removed under reduced pressure
  7. customto afford a crude brown oil, which
  8. customwas purified by column chromatography (SiO2)
  9. washeluting with 0-20% EtOAc/hexanes

Sources & evidence

ORD record
ord-c30122a171c146d091ae840147797e64
Source dataset
uspto-grants-2013_07
Patent number
US08481524B2

Reaction notes

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