Potassium Phosphate, Tribasic → HCID 86685342, compound

HRID 1853084Notes

Reaction equation

HRID 1853084 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([C:13]3([CH2:24][C:25]#[N:26])[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]3)[CH:12]=2)[N:5]2[CH:27]=[CH:28][N:29]=[C:4]2[CH:3]=1.[CH3:30][O:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CCOC(C)=O.C([O-])(O)=O.[Na+].C(Cl)Cl.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].CO>[C:25]([CH2:24][C:13]1([N:11]2[CH:12]=[C:8]([C:6]3[N:5]4[CH:27]=[CH:28][N:29]=[C:4]4[CH:3]=[C:2]([C:35]4[CH:36]=[CH:37][C:32]([O:31][CH3:30])=[CH:33][CH:34]=4)[N:7]=3)[CH:9]=[N:10]2)[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]1)#[N:26]

Participants

11

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86685321HCID 86685321, compound

Product 1

HCID 86685342HCID 86685342, compoundYield 104.3%

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
75 °C

Procedure

tert-Butyl 3-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-(cyanomethyl)azetidine-1-carboxylate (Preparation N; 2.80 g, 6.76 mmol), 4-methoxybenzeneboronic acid (1.54 g, 10.1 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.644 g, 1.35 mmol) and K3PO4 (10.1 mL, 20.3 mmol) were suspended in 1,4-dioxane (30 mL) and purged with Ar (g). Pd2dba3 (0.619 g, 0.676 mmol) was added and the system sealed and heated at 75° C. overnight. The reaction mixture was diluted with EtOAc and saturated aqueous NaHCO3. The bi-phasic mixture was passed through a pad of Celite® to remove solids. The Celite® was washed with DCM and MeOH. The organic layer was separated and then washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford some crude material. This was combined with the DCM and MeOH washed off the Celite® to afford the crude total material. The crude material was suspended in DCM to load onto a column. Many solids did not dissolve and were collected and identified as desired crude material. The crude material was loaded onto a column and purified by flash column chromatography, eluting with 2-4% (9:1 MeOH:NH4OH)/DCM to provide tert-butyl 3-(cyanomethyl)-3-(4-(7-(4-methoxyphenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (3.42 g, 7.044 mmol, 104.3% yield). MS (apci) m/z=486.2 (M+H).

Workup

  1. custompurged with Ar (g)
  2. customthe system sealed
  3. customto remove solids
  4. washThe Celite® was washed with DCM and MeOH
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford some crude material
  11. washwashed off the Celite®
  12. customto afford the crude total material
  13. dissolutionMany solids did not dissolve
  14. customwere collected
  15. custompurified by flash column chromatography
  16. washeluting with 2-4% (9:1 MeOH:NH4OH)/DCM

Sources & evidence

ORD record
ord-316fb43db8ab4153a8e85533867d9aae
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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