Potassium Phosphate, Tribasic → Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylate

HRID 908383Notes

Reaction equation

HRID 908383 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:27]1[C:28]([CH3:45])=[N:29][N:30]([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)[CH:31]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:25][C:11]1[N:12]=[CH:13][C:14]([C:27]2[C:28]([CH3:45])=[N:29][N:30]([CH:32]3[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[O:39])[CH2:36][CH2:37]3)[CH:31]=2)=[CH:15][C:10]=1[C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 58293746Tert-butyl 4-(4-bromo-3-methyl-pyrazol-1-yl)piperidine-1-carboxylateHCID 673889123-(1,3-Benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 57687030Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylateYield 65.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (600 mg), tert-butyl 4-(4-bromo-3-methyl-pyrazol-1-yl)piperidine-1-carboxylate (557 mg), tris(dibenzylideneacetone)dipalladium (74.1 mg), tricyclohexylphosphine (45.4 mg) and potassium phosphate (584 mg) in 1,4-dioxane (3.4 mL) and water (0.4 mL) was degassed with argon, then stirred at 100° C. for 3 h under argon. Solvents were removed. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 5 to 10% methanol in dichloromethane. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylate (500 mg); NMR Spectrum: (DMSOd6) 1.43 (s, 9H), 1.78 (dd, 1H), 1.83 (dd, 1H), 1.99-2.07 (m, 2H), 2.33 (s, 3H), 2.91 (bs, 2H), 4.01-4.11 (m, 2H), 4.24-4.32 (m, 1H), 7.42-7.50 (m, 2H), 7.65 (bs, 2H), 7.77-7.83 (m, 2H), 8.10 (s, 1H), 8.29 (d, 1H), 8.35 (d, 1H); Mass spectrum: M+H+: 475

Workup

  1. customwas degassed with argon
  2. customSolvents were removed
  3. custompurified by flash chromatography on silica gel eluting with 5 to 10% methanol in dichloromethane
  4. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-5dd1ce36c1a6469e9ea978fef656c956
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

Loading…