Potassium Carbonate → HCID 178432608, compound

HRID 1530605Notes

Reaction equation

HRID 1530605 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH3:20])[C:6]=1[CH:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1.[CH3:21][C:22]1[N:26]=[C:25]([C:27]2[N:28]=[C:29]3[N:39]([CH:40]=2)[CH2:38][CH2:37][O:36][C:35]2[C:30]3=[CH:31][CH:32]=[C:33](B(O)O)[CH:34]=2)[N:24]([CH:44]([CH3:46])[CH3:45])[N:23]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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]>[C:16]([O:15]1[CH2:10][CH2:11][CH2:12][CH:7]([C:6]2[N:5]([CH3:20])[N:4]=[CH:3][C:2]=2[C:33]2[CH:34]=[C:35]3[C:30](=[CH:31][CH:32]=2)[C:29]2[N:39]([CH:40]=[C:27]([C:25]4[N:24]([CH:44]([CH3:45])[CH3:46])[N:23]=[C:22]([CH3:21])[N:26]=4)[N:28]=2)[CH2:38][CH2:37][O:36]3)[CH2:8][NH:9][C:13]1=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 68313095{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}boronic acidHCID 68313245tert-Butyl 3-(4-bromo-1-methyl-1H-pyrazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 178432608HCID 178432608, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 3-(4-bromo-1-methyl-1H-pyrazol-5-yl)piperidine-1-carboxylate (680 mg, 1.98 mmol) in dioxane (20.0 mL), was added {4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}boronic acid (660 mg, 1.87 mmol), K2CO3 (780 mg, 5.70 mmol), and Pd(dppf)Cl2 (117 mg, 0.19 mmol). The resulting mixture was stirred at 80° C. for 18 h. After concentration, the residue was diluted with EtOAc (20 mL) and washed with brine (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography eluting with a 0-20% gradient of EtOAc in petroleum ether to give 1-tert-butyl-5-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)-λ3,3-oxazocan-2-one (540 mg, 50% yield) as a yellow solid. LCMS (ESI) m/z: 573.4 [M+H+].

Workup

  1. concentrationAfter concentration
  2. additionthe residue was diluted with EtOAc (20 mL)
  3. washwashed with brine (20 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a 0-20% gradient of EtOAc in petroleum ether

Sources & evidence

ORD record
ord-ef324a77f44e4cc7ba8b2b9c9d19269e
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…