Sodium Bicarbonate → HCID 67377517, compound

HRID 1896080Notes

Reaction equation

HRID 1896080 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[N:12]([C:13]3[CH:32]=[CH:31][C:16]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[C:15]([F:33])[C:14]=3[F:34])[N:11]=[N:10][N:9]=2)=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1.C([O-])(O)=O.[Na+]>CN(C=O)C.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]>[NH2:1][C:2]1[C:7]([C:8]2[N:12]([C:13]3[CH:32]=[CH:31][C:16]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[C:15]([F:33])[C:14]=3[F:34])[N:11]=[N:10][N:9]=2)=[CH:6][C:5]([C:40]2[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67376812HCID 67376812, compound2×

Product 1

HCID 67377517HCID 67377517, compoundYield 50%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

As shown in step 4-v of Scheme 4, tert-butyl 4-(4-(5-(2-amino-5-bromopyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenoxy)butylmethylcarbamate (Compound 1019, 554 mg, 1.00 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (250 mg, 1.20 mmol) were dissolved in 8.0 mL of DMF and 4.0 mL of saturated NaHCO3 (aq) were added. The mixture was flushed with argon gas for 1 hour and PdCl2(dppf) (43.2 mg, 53.0 mmol) was added. The reaction mixture was flushed with argon for an additional 30 minutes followed by heating to 100° C. for 1 hour. After cooling, the mixture was diluted with EtOAc (80 mL), washed with water (3×40 mL), washed with brine (40 mL), and dried over sodium sulfate. After filtration, the organics were concentrated under reduced pressure and the residue purified by silica gel chromatography (40% EtOAc/hexanes) to provide tert-butyl 4-(4-(5-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenoxy)butylmethylcarbamate (278 mg, 50% yield), which was used as is in subsequent reactions.

Workup

  1. customThe mixture was flushed with argon gas for 1 hour
  2. customThe reaction mixture was flushed with argon for an additional 30 minutes
  3. temperatureAfter cooling
  4. additionthe mixture was diluted with EtOAc (80 mL)
  5. washwashed with water (3×40 mL)
  6. washwashed with brine (40 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe organics were concentrated under reduced pressure
  10. customthe residue purified by silica gel chromatography (40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a3ff210b69d14fe79a6f2a06eac17b52
Source dataset
uspto-grants-2013_08
Patent number
US08518938B2

Reaction notes

Loading…