Potassium Carbonate → 7-[(R)-1-(2,6-Dichloro-3-fluorophenyl)-ethoxy]-3-(1-methyl-1H-pyrazol-4-yl)-furo[3,2-c]pyridin-6-ylamine

HRID 911954Notes

Reaction equation

HRID 911954 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.[CH3:24][N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:22][C:15]1[C:16]([F:21])=[CH:17][CH:18]=[C:19]([Cl:20])[C:14]=1[C@H:12]([O:11][C:10]1[C:5]2[O:4][CH:3]=[C:2]([C:28]3[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=3)[C:6]=2[CH:7]=[N:8][C:9]=1[NH2:23])[CH3:13]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 441815357-[(R)-1-(2,6-Dichloro-3-fluorophenyl)-ethoxy]-3-(1-methyl-1H-pyrazol-4-yl)-furo[3,2-c]pyridin-6-ylamineYield 39.7%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 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 (40 mg, 0.095 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (30 mg, 0.14 mmol), and potassium carbonate (39 mg, 0.28 mmol) in 1,4-dioxane (1.5 mL) and H2O (0.5 mL) was degassed and refilled with argon (3×) prior to addition of (1,1′-bis(diphenylphosphino)-ferrocene) palladium dichloride (7.0 mg, 0.0095 mmol). The reaction mixture was degassed and refilled with argon (2×) and stirred at 100° C. for 30 min in a CEM microwave. LC-MS showed completion of the reaction. The mixture was diluted with EtOAc (30 mL), washed with brine (10 mL), and dried over anhydrous sodium sulfate. The residue was purified by mass-directed purification to give the title compound as a brown oil (15.9 mg). 1H NMR (CDCl3, 400 MHz): δ=1.91 (d, J=6.8 Hz, 3H), 4.00 (s, 3H), 5.93 (br s, 2H), 6.65 (q, J=6.8 Hz, 1H), 7.09 (dd, J=9.1, 7.8 Hz, 1H), 7.31 (dd, J=9.1, 4.8 Hz, 1H), 7.58 (s, 1H), 7.64 (s, 1H), 7.71 (s, 1H), 8.03 (s, 1H). MS (ES+): 421.00/423.02 [MH+].

Workup

  1. customwas degassed
  2. additionrefilled with argon (3×)
  3. customThe reaction mixture was degassed
  4. additionrefilled with argon (2×)
  5. customcompletion of the reaction
  6. washwashed with brine (10 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe residue was purified by mass-directed purification

Sources & evidence

ORD record
ord-6c7283b80a3b4549bb21c2c1b1cdc431
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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