Potassium Phosphate, Tribasic → 9-cyclopentyl-N-(6-(4-pyridinyl)-3-pyridazinyl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 876062Notes

Reaction equation

HRID 876062 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[N:20][C:19](Cl)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:23]=[CH:24][N:25]=[CH:26][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[N:20][C:19]([C:30]5[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=5)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:23]=[CH:24][N:25]=[CH:26][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2734379(Pyridin-4-yl)boronic acidHCID 582996836-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-chloro-pyridazine

Product 1

HCID 582999279-cyclopentyl-N-(6-(4-pyridinyl)-3-pyridazinyl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 28.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of compound 140 (199 mg, 544 μmol) in dioxane (3 mL) were added pyridin-4-ylboronic acid (66.9 mg, 544 μmol), Pd2(dba)3 (24.9 mg, 27.2 μmol), tricyclohexylphosphine (15.3 mg, 54.4 μmol), and potassium phosphate (231 mg, 1.09 mmol) (in 1 mL of water). The reaction mixture was purged with N2 for 20 minutes and the reaction was heated at 100° C. degree for 18 hours. DCM was added to the reaction and the mixture was washed with water and brine. The organic layer was dried with sodium sulfate. The product was purified using Combiflash (DCM/methanol) followed by trituration with ethyl acetate to give compound 415 as a yellow solid (63 mg, 28%). 1H NMR (500 MHz, CD2Cl2) δ ppm 9.25 (1 H, s), 8.97-9.05 (2 H, m), 8.92 (1 H, s), 8.79 (2 H, d, J=6.1 Hz), 8.57 (1 H, d, J=5.1 Hz), 8.00-8.08 (3 H, m), 7.96 (1 H, dd, J=5.1, 1.2 Hz), 5.48 (1 H, quin, J=8.9 Hz), 2.48 (2 H, m), 2.20-2.28 (4 H, m), 1.95 (2 H, dddd, J=8.2, 4.5, 4.3, 4.2 Hz), 1.63 (2 H, br. s.); LCMS-ESI (POS), M/Z, M+1: Found 409.1, Calculated 409.2.

Workup

  1. customThe reaction mixture was purged with N2 for 20 minutes
  2. additionDCM was added to the reaction
  3. washthe mixture was washed with water and brine
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. customThe product was purified

Sources & evidence

ORD record
ord-fcc575d49a2b447ba489af8b20478e78
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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