(S)-1,2-Dimethylpiperazine → HCID 135566983, compound
Reaction equation
C[C@H]1CNCCN1C.Cc1cc(Cl)ncc1-c1ccc(-c2nc3c(CO)cccc3c(=O)[nH]2)cc1>C1COCCO1.CC(C)(C)[O-].CC(C)Oc1cccc(OC(C)C)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1.CC(C)Oc1cccc(OC(C)C)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1.COC(C)(C)C.NCCc1[c-]cccc1.[Cl][Pd+].[Na+]>Cc1cc(N2CCN(C)[C@@H](C)C2)ncc1-c1ccc(-c2nc3c(CO)cccc3c(=O)[nH]2)cc1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 115 °C
Procedure
A mixture of CHLORO(2-DICYCLOHEXYLPHOSPHINO-2',6'-DI-I- PROPOXY-1,1'-BIPHENYL)[2-(2-AMINOETHYLPHENYL)]PALLADIUM(II), METHYL-T- BUTYLETHER ADDUCT (Ru Phos Pd cycle) (69.2 mgs, 0.2eq), sodium tert-butoxide (244 mg, 2.54 mmol) ,2-(4-(6-chloro-4-methylpyridin-3-yl)phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one (200 mg, 0.42 mmol) , (S)-1,2-dimethylpiperazine (198 mg, 1.06 mmol) in dioxane (20ml) was stirred at 115°C for 1hr, LCMS indicated the completion of reaction. The solid was filtered off through a pad of celite, washed with DCM. The solvent of the filtrate was removed by concentration, taken into 2ml of DMSO, purified with reverse phase chromatography column (eluted with 5% to 50% 0.1%TFA in ACN/0.1%TFA in water), the fractions were combined and lyphlized, to yield 117mgs of product. LCMS indicated 9% of TFA coupled side product. The solid was taken into 10ml sat. NaHCO3 aq, sonicated, until the disapearance of the side product, filtered, washed with water, dried to yield (S)-2-(4-(6-(3,4-dimethylpiperazin-1-yl)-4-methylpyridin-3-yl)phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one (67.0 mg, 34.7 %) as a yellow solid.
Sources & evidence
- ORD record
- ord-135c33d2da2b4d7f90276e4b49e654c9
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Reaction notes
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