Water → 3-[4-(2-chloro-5-methoxypyrimidin-4-yl)-1H-pyrazol-1-yl]-3-cyclopropylpropanenitrile

HRID 1876896Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([O:9][CH3:10])=[CH:4][N:3]=1.[CH:11]1([CH:14]([N:18]2[CH:22]=[C:21](B3OC(C)(C)C(C)(C)O3)[CH:20]=[N:19]2)[CH2:15][C:16]#[N:17])[CH2:13][CH2:12]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1.O>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:21]2[CH:20]=[N:19][N:18]([CH:14]([CH:11]3[CH2:13][CH2:12]3)[CH2:15][C:16]#[N:17])[CH:22]=2)[C:5]([O:9][CH3:10])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2,4-dichloro-5-methoxypyrimidine (from Aldrich Chemicals, 1.47 g, 0.00821 mol), 3-cyclopropyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (from example 177 step 1, 2.34 g, 0.00815 mol), tetrakis(triphenylphosphine)palladium(0) (0.6 g, 0.0005 mol), and potassium phosphate (5.2 g, 0.025 mol) in 1,4-dioxane (20 mL, 0.3 mol) and water (2 mL, 0.1 mol) was heated at 100° C. overnight. After cooling to room temperature, the mixture was dilute with AcOEt, washed with water, brine, dried over MgSO4, concentrated. The residue was purified on silica gel, eluting with 0 to 60%, to give the desired product (580 mg, 23.43%). LCMS (M+H) 304.3

Workup

temperatureAfter cooling to room temperature
washwashed with water, brine
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue was purified on silica gel
washeluting with 0 to 60%

Sources & evidence

ORD record: ord-14b848bfdcea4116a5612e4be3f84866
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309718B2

Reaction notes

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