Potassium Carbonate → HCID 178455333, compound

HRID 389605Notes

Reaction equation

HRID 389605 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[N:24][C:23]([NH2:26])=[C:22]4[O:27][C:28](Cl)=[CH:29][C:21]=34)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:31][C:32]([F:47])([F:46])[C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[F:31][C:32]([F:46])([F:47])[C:33]1[CH:34]=[C:35]([C:28]2[O:27][C:22]3=[C:23]([NH2:26])[N:24]=[CH:25][C:20]([C:18]4[CH:17]=[N:16][N:15]([C@H:12]5[CH2:13][CH2:14][C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10][CH2:11]5)[CH:19]=4)=[C:21]3[CH:29]=2)[CH:36]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:38]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1562653,5-Bis-trifluoromethylphenylboronic acidHCID 178455334HCID 178455334, compound

Product 1

HCID 178455333HCID 178455333, compoundYield 92.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chlorofuro[2,3-c]pyridin-7-amine (83 mg, 0.18 mmol), 3,5-bis(trifluoromethyl)benzeneboronic acid (71 mg, 0.28 mmol), (1,1′-bis-(diphenylphosphino)ferrocene)palladium dichloride (13.5 mg, 0.0186 mmol), and potassium carbonate (77 mg, 0.56 mmol) in 1,4-dioxane (1.0 mL) and water (0.30 mL) was degassed 3× with argon and heated in a microwave reactor at 100° C. for 1 h. The mixture was partitioned between EtOAc and brine and the aqueous phase was extracted with EtOAc. The combined organic fractions were dried over sodium sulfate and concentrated. Purification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM) afforded 104 mg (90%) of the title compound as a foam. 1H NMR (400 MHz, CDCl3): δ 0.06-0.14 (m, 6H) 0.87-0.98 (m, 9H) 1.49-1.64 (m, 2H) 1.85-2.11 (m, 4H) 2.18-2.33 (m, 2H) 3.69-3.82 (m, 2H), 4.17-4.28 (m, 1H), 5.05 (br. s., 1H) 7.34 (s, 1H) 7.70 (s, 1H) 7.82 (s, 1H) 7.92 (s, 1H) 8.00 (s, 1H) 8.31 (s, 2H); MS (ESI): 624.34 [M+H]+; HPLC tR=2.00 min (TOF: nonpolar—3 min).

Workup

  1. customwas degassed 3× with argon
  2. customThe mixture was partitioned between EtOAc and brine
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialThe combined organic fractions were dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM)

Sources & evidence

ORD record
ord-d111da58ca0e49f49745af4974f11769
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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