Potassium Carbonate → HCID 57812309, compound

HRID 911991Notes

Reaction equation

HRID 911991 reaction equation
Br[C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]3[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=3[Cl:22])[CH3:13])[C:5]=2[O:4][CH:3]=1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([N:37]2[CH:41]=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:39]=[N:38]2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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:24]([O:28][C:29]([N:31]1[CH2:32][CH2:33][CH:34]([N:37]2[CH:41]=[C:40]([C:2]3[C:6]4[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]5[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=5[Cl:22])[CH3:13])[C:5]=4[O:4][CH:3]=3)[CH:39]=[N:38]2)[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 57812309HCID 57812309, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-6-ylamine (601 mg, 1.43 mmol), 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (810 mg, 2.1 mmol) and potassium carbonate (590 mg, 4.3 mmol) in 1,4-dioxane (10 mL) and H2O (3 mL) was degassed and refilled with argon (3×) prior to the addition of PdCl2(dppf) (105 mg, 0.143 mmol). The reaction mixture was degassed and refilled with argon (2×) and heated at 100° C. for 2 h (conventional heating). The mixture was diluted with EtOAc (60 mL), then washed with brine (20 mL), and dried over anhydrous sodium sulfate. The residue was purified by silica gel chromatography (Hex:EtOAc=50:50→20:80→100% EtOAc) to give the title compound as a light-yellow solid. LC-MS (ES+): 590.07/592.09 [MH+]. 1H NMR (CDCl3, 400 MHz): δ 1.49 (s, 9H), 1.90 (d, J=6.8 Hz, 3H), 1.91-2.02 (m, 2H), 2.17-2.20 (m, 2H), 2.93 (m, 2H), 4.27-4.36 (m, 3H), 5.24 (br s, 2H), 6.62 (q, J=6.8 Hz, 1H), 7.07 (dd, J=8.8, 7.8 Hz, 1H), 7.30 (dd, J=8.8, 4.8 Hz, 1H), 7.55 (s, 1H), 7.68 (s, 1H), 7.75 (s, 1H), 8.11 (s, 1H).

Workup

  1. customwas degassed
  2. additionrefilled with argon (3×)
  3. customThe reaction mixture was degassed
  4. additionrefilled with argon (2×)
  5. temperature(conventional heating)
  6. additionThe mixture was diluted with EtOAc (60 mL)
  7. washwashed with brine (20 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe residue was purified by silica gel chromatography (Hex:EtOAc=50:50→20:80→100% EtOAc)

Sources & evidence

ORD record
ord-13ef7ace072543caa54674e8904868f2
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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