Dimethylformamide → HCID 57812684, compound

HRID 912008Notes

Reaction equation

HRID 912008 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.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[CH:34][C:35]([N:38]3[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]3)=[N:36][CH:37]=2)O1.C(=O)([O-])[O-].[K+].[K+].ClCCl.C[Si]([N:58]=[C:59]=[O:60])(C)C.CCN(C(C)C)C(C)C.CN(C=O)C>O1CCOCC1.O.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[Pd]Cl>[NH2:23][C:9]1[N:8]=[CH:7][C:6]2[C:2]([C:32]3[CH:33]=[CH:34][C:35]([N:38]4[CH2:39][CH2:40][N:41]([C:59]([NH2:58])=[O:60])[CH2:42][CH2:43]4)=[N:36][CH:37]=3)=[CH:3][O:4][C:5]=2[C:10]=1[O:11][C@@H:12]([C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=1[Cl:22])[CH3:13]

Participants

12

Reactant 7

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 162179462-(Piperazin-1-yl)pyridine-5-boronic acid, pinacol esterHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 57812684HCID 57812684, compound

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine (15.0 mg, 0.0357 mmol, 1 eq.), 1-[5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (20.6 mg, 0.0714 mmol, 2 eq.), potassium carbonate (14.8 mg, 0.107, 3 eq.) in dioxane (0.9 mL) and water (0.3 mL) was added 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1 mg, 0.002 mmol, 0.05 eq.). The mixture was evacuated by vacuum and filled with nitrogen 3 times and heated in a microwave reactor at 100° C. for 30 min. The crude mixture was dried in vacuo, and trimethylsilyl isocyanate (14.5 uL, 0.107 mmol), DIPEA (62.2 uL, 0.357 mmol), and DMF (0.2 mL, 2 mmol) were added. The resulting mixture was stirred at room temperature overnight. The crude solution was passed through Thiol-SPE to remove palladium. The solution was further passed through SCX-2 SPE and the product was released by 2M NH3 in methanol. The solution was concentrated, dissolved in DMSO, and purified on the MDPS. MS (ES+): m/z 545.17/547.17 (100/76) [MH+]. HPLC: tR=0.71 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, DMSO-d6): δ=1.83 (d, J=6.8 Hz, 3H), 3.49-3.57 (m, 8H), 5.63 (s, 2H), 6.07 (s, 2H), 6.27 (q, J=6.7 Hz, 1H), 6.96 (d, J=8.8 Hz, 1H), 7.46 (t, J=8.7 Hz, 1H), 7.53 (dd, J=9.0, 4.9 Hz, 1H), 7.87 (dd, J=8.7, 2.1 Hz, 1H), 8.04 (s, 1H), 8.28 (s, 1H), 8.48 (d, J=2.5 Hz, 1H).

Workup

  1. customThe mixture was evacuated by vacuum
  2. additionfilled with nitrogen 3 times
  3. additionwere added
  4. customto remove palladium
  5. concentrationThe solution was concentrated
  6. dissolutiondissolved in DMSO
  7. custompurified on the MDPS

Sources & evidence

ORD record
ord-2b1ada5b8e2843389d15af0cf886dff3
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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