Acetonitrile → (R)-1-(4-(2-(5-fluoro-2-methoxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one

HRID 2062201Notes

Reaction equation

HRID 2062201 reaction equation
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:25])[C@H:19]([OH:24])[CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([CH3:26])=[CH:7][CH:8]=2)[N:3]=1.[F:27][C:28]1[CH:29]=[CH:30][C:31]([O:37][CH3:38])=[C:32](B(O)O)[CH:33]=1.C([O-])([O-])=O.[K+].[K+].C(#N)C>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.O>[F:27][C:28]1[CH:33]=[CH:32][C:31]([O:37][CH3:38])=[C:30]([C:2]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][N:15]([C:18](=[O:25])[C@H:19]([OH:24])[CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:14][CH2:13]3)[C:9]3[C:4](=[CH:5][C:6]([CH3:26])=[CH:7][CH:8]=3)[N:3]=2)[CH:29]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 58010811(R)-1-(4-(2-chloro-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one

Product 1

HCID 58010783(R)-1-(4-(2-(5-fluoro-2-methoxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-oneYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

(R)-1-(4-(2-Chloro-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one (50 mg, 0.13 mmol), 5-fluoro-2-methoxyphenylboronic acid (27 mg, 0.16 mmol), Pd(Ph3P)4 (9.2 mg, 0.008 mmol), and K2CO3 (37 mg, 0.27 mmol) were placed into a microwave tube charged with a stir bar. Acetonitrile (2 mL) and H2O (400 μL) were added, and the vessel was capped and heated at 160° C. for 12 minutes in the microwave reactor. The reaction was partitioned between EtOAc and H2O, the layers were separated, and the aqueous layer was extracted once more with EtOAc. The organic extracts were combined, dried over Na2SO4, filtered, and concentrated to an orange gel. The reaction was purified by silica gel chromatography using 10%-30% EtOAc in CH2Cl2/hexanes (2:1) to afford (R)-1-(4-(2-(5-fluoro-2-methoxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one as a white foam (70%). LC/MS: m/z 467.30 (M+H)+ at 2.38 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. additioncharged with a stir bar
  2. customthe vessel was capped
  3. customThe reaction was partitioned between EtOAc and H2O
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted once more with EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an orange gel
  9. customThe reaction was purified by silica gel chromatography

Sources & evidence

ORD record
ord-62813b5e451948b18cde43f6e0d293de
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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