Dichloromethane → 5-[1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl]pyrimidin-2-amine

HRID 1257861Notes

Reaction equation

[O:1]1[CH2:5][CH2:4][CH:3]([N:6]2[CH:10]=[C:9](B3OC(C)(C)C(C)(C)O3)[CH:8]=[N:7]2)[CH2:2]1.Br[C:21]1[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.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].O.CCO>[O:1]1[CH2:5][CH2:4][CH:3]([N:6]2[CH:10]=[C:9]([C:21]3[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=3)[CH:8]=[N:7]2)[CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 1-(Tetrahydrofuran-3-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (110 mg, 0.42 mmol) in 1,4-dioxane (3 mL) was added EtOH (1 mL) and water (0.4 mL). The following reagents were added successively: 5-bromopyrimidin-2-amine (75 mg, 0.43 mmol), potassium carbonate (180 mg, 1.3 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (20 mg, 0.02 mmol). The vessel was purged several times with N2 and heated to 100° C. for 4 h. The reaction mixture was filtered through a pad of Celite, concentrated, and purified by chromatography on silica gel (40 g column, 0-15% MeOH/methylene chloride) to afford the desired product. LCMS: (M+H)=232.0.

Workup

additionThe following reagents were added successively
customThe vessel was purged several times with N2
filtrationThe reaction mixture was filtered through a pad of Celite
concentrationconcentrated
custompurified by chromatography on silica gel (40 g column, 0-15% MeOH/methylene chloride)

Sources & evidence

ORD record: ord-ebf0b022a0df4f7abf62dc4e1463152a
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461330B2

Reaction notes

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