Dichloromethane → HCID 118598587, compound

HRID 1050370Notes

Reaction equation

HRID 1050370 reaction equation
ClC1C=C(N[C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15]C(C3CC3)=O)[CH:10]=2)C(=O)N2C(C3C=CC=C(F)C=3)(C)NC(=O)C=12.ClC1C=[C:39]([N:41](CC2C=CC(OC)=CC=2)[C:42]2[CH:47]=[CH:46][N:45]=CN=2)C(=O)N2C3(CCCCC3)N(CC3C=CC(OC)=CC=3)C(=O)C=12.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>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]>[CH3:39][N:41]1[CH:42]=[C:47]([C:10]2[C:11]([NH2:15])=[N:12][CH:13]=[N:14][CH:9]=2)[CH:46]=[N:45]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 118598561HCID 118598561, compoundHCID 118599037HCID 118599037, compound

Product 1

HCID 118598587HCID 118598587, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-iodopyrimidin-4-amine (1, 0.5 g, 2.26 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (2, 0.56 g, 2.71 mmol) in dioxane/water (15 mL, 9:1.5) in a vial, was added cesium carbonate (1.84 g, 5.66 mmol) and the mixture was degassed with argon for 15 min. To this mixture was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.09 g, 0.11 mmol) and then heated to 110° C. for 16 h. TLC showed consumption of starting material, cooled the reaction mixture to ambient temperature, filtered the mass over celite bed, washed with dichloromethane (30 mL) followed by concentration of filtrate. The crude compound was purified by flash column chromatography eluting with 3% methanol in dichloromethane. The desired fractions were concentrated to dryness to afforded as 5-(1-methylpyrazol-4-yl)pyrimidin-4-amine (3) as off white solid; Yield: 0.2 g, 50%; MS (ESI) m/z 176.08 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 8.13 (s, 1H), 8.01 (s, 1H), 7.70 (s, 1H), 6.61 (s, 2H), 3.87 (s, 3H).

Workup

  1. customthe mixture was degassed with argon for 15 min
  2. customconsumption of starting material
  3. temperaturecooled the reaction mixture to ambient temperature
  4. filtrationfiltered the mass over celite bed
  5. washwashed with dichloromethane (30 mL)
  6. customThe crude compound was purified by flash column chromatography
  7. washeluting with 3% methanol in dichloromethane
  8. concentrationThe desired fractions were concentrated to dryness

Sources & evidence

ORD record
ord-f98a904cbfbd45f8adfb8f764021ab6b
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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