Potassium Phosphate, Tribasic → tert-butyl 4-(4-(3-(difluoromethyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-2-methoxyphenyl)piperazine-1-carboxylate

HRID 2209087Notes

Reaction equation

HRID 2209087 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]2[CH2:15][NH:14][C:13](=[O:16])[CH2:12]2)[CH3:10])[C:5]2[N:17]([CH:20]([F:22])[F:21])[CH:18]=[N:19][C:4]=2[CH:3]=1.[CH3:23][O:24][C:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[N:40]1[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[F:21][CH:20]([F:22])[N:17]1[C:5]2[C:6]([O:8][C@@H:9]([C@@H:11]3[CH2:12][C:13](=[O:16])[NH:14][CH2:15]3)[CH3:10])=[N:7][C:2]([C:29]3[CH:28]=[CH:27][C:26]([N:40]4[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:50])([CH3:51])[CH3:52])=[O:47])[CH2:42][CH2:41]4)=[C:25]([O:24][CH3:23])[CH:30]=3)=[CH:3][C:4]=2[N:19]=[CH:18]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 89494488Tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylateHCID 117842863(R)-4-((R)-1-(6-chloro-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117843882tert-butyl 4-(4-(3-(difluoromethyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-2-methoxyphenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2.64 (102 mg, 0.308 mmol), tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate 7.08 (160 mg, 0.38 mmol), K3PO4 (191 mg, 0.9 mmol) and Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium (II) (7.2 mg, 0.01 mmol) were taken up in 1,4-dioxane (4.4 mL) and water (0.44 mL). The stirred reaction mixture was heated to 100° C. for 1.5 h and was then cooled and partitioned between EtOAc, water and brine. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (0-15% MeOH in DCM) to provide tert-butyl 4-(4-(3-(difluoromethyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-2-methoxyphenyl)piperazine-1-carboxylate. LCMS-ESI+ (m/z): [M+H]+ calcd for C29H37F2N6O5: 587.3; found: 587.2.

Workup

  1. customThe stirred reaction mixture
  2. temperaturewas then cooled
  3. custompartitioned between EtOAc, water and brine
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with EtOAc
  6. dry with materialThe combined organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography (0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-018da3a99c874286b93a5a343a997a07
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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