Sodium Carbonate → HCID 86662408, compound

HRID 389488Notes

Reaction equation

HRID 389488 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]1[CH:4]=[C:5]([C:13]2[O:23][C:16]3=[C:17]([NH2:22])[N:18]=[CH:19][C:20](Br)=[C:15]3[CH:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][N:37]([CH:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]3)[CH:38]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:22][C:17]1[N:18]=[CH:19][C:20]([C:34]2[CH:35]=[N:36][N:37]([CH:39]3[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:43][CH2:44]3)[CH:38]=2)=[C:15]2[CH:14]=[C:13]([C:5]3[CH:4]=[C:3]([C:2]([F:25])([F:24])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=3)[O:23][C:16]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 86662409HCID 86662409, compound

Product 1

HCID 86662408HCID 86662408, compoundYield 36.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 2-(3,5-bis-trifluoromethyl-phenyl)-4-bromo-furo[2,3-c]pyridin-7-ylamine (0.449 g, 1.06 mmol) and tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (0.419 g, 1.11 mmol) in 1,4-dioxane (60 mL) and water (12 mL) was stirred for 10 min and degassed with nitrogen for 15 min. To this stirred mixture was added Pd(PPh3)2Cl2 (100 mg, 0.14 mmol) and the solution was degassed with nitrogen for an additional 5 min. Na2CO3 (168 mg, 1.59 mmol) was added and resulting mixture was stirred at 95° C. for 4 h. The reaction mixture was cooled to RT and the solvent was removed on a rotary evaporator to give the crude compound, which was purified by flash chromatography (2% MeOH:DCM) to afford 229 mg (36%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.45 (s, 9H), 2.10 (m, 2H), 2.22 (m, 2H), 2.97 (t, J=13.2 Hz, 2H), 4.35 (m, 3H), 5.59 (br, 2H), 7.34 (s, 1H), 7.71 (s, 1H), 7.81 (s, 1H), 7.92 (d, J=5.1 Hz, 2H), 8.32 (s, 2H). MS (ESI): 596 [M+H]+.

Workup

  1. customdegassed with nitrogen for 15 min
  2. customthe solution was degassed with nitrogen for an additional 5 min
  3. customresulting mixture
  4. temperatureThe reaction mixture was cooled to RT
  5. customthe solvent was removed on a rotary evaporator
  6. customto give the crude compound, which
  7. customwas purified by flash chromatography (2% MeOH:DCM)

Sources & evidence

ORD record
ord-e1c9ce2aed1846609400ddbc05f64270
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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