Sodium Bicarbonate → HCID 58293764, compound

HRID 446742Notes

Reaction equation

HRID 446742 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([F:21])[C:15]=3[F:22])[N:12]=[N:11][N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[N:33][N:34]([CH:36]3[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]3)[CH:35]=2)O1.C(=O)(O)[O-].[Na+]>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].COCCOC>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:31]2[CH:32]=[N:33][N:34]([CH:36]3[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40][CH2:41]3)[CH:35]=2)=[CH:3][C:4]=1[C:9]1[N:13]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([F:21])[C:15]=2[F:22])[N:12]=[N:11][N:10]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate2×HCID 58293756HCID 58293756, compound2×

Product 1

HCID 58293764HCID 58293764, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

A round-bottom flask was charged with 5-bromo-3-(1-(2,3-difluoro-4-methylphenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1073, 3.672 g, 10 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (Compound 1098, 4.150 g, 11.00 mmol) and DME (100 mL) was bubbled with nitrogen gas for 20 min. A 1.2 M aqueous solution of sodium bicarbonate (25.00 mL, 30.00 mmol) was added and nitrogen flow was continued for another 40 min before addition of PdCl2(dppf)2 (731.7 mg, 1.000 mmol). The suspension was heated at 70° C. for 15 hours, filtered though a layer of diatomaceous earth, and the filtrate washed with brine. The volatiles were removed by vacuum evaporation to afford a residue that was purified by silica gel chromatography, eluting with 20-100% EtOAc/hexanes, to produce tert-butyl 4-(4-(6-amino-5-(1-(2,3-difluoro-4-methylphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate as a yellow solid (Compound 1102, 4.0 g, 74%).

Workup

  1. customwas bubbled with nitrogen gas for 20 min
  2. filtrationfiltered though a layer of diatomaceous earth
  3. washthe filtrate washed with brine
  4. customThe volatiles were removed by vacuum evaporation
  5. customto afford a residue that
  6. customwas purified by silica gel chromatography
  7. washeluting with 20-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-dab371f5e9d045c5b93ebd371fdd20d9
Source dataset
uspto-grants-2013_07
Patent number
US08481524B2

Reaction notes

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