Cesium carbonate → HCID 59519096, compound

HRID 1161857Notes

Reaction equation

HRID 1161857 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:48]1[CH:49]=[C:50]2[C:55](=[CH:56][CH:57]=1)[N:54]=[C:53]([C:58]1[CH:63]=[CH:62][CH:61]=[C:60]([Cl:64])[CH:59]=1)[N:52]([CH2:65][C:66]([NH:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[C:51]2=[O:73].[C:74]([O:78][C:79]([N:81]1[CH2:87][CH2:86][CH2:85][NH:84][CH2:83][CH2:82]1)=[O:80])([CH3:77])([CH3:76])[CH3:75].C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.C1(C)C=CC=CC=1>[C:74]([O:78][C:79]([N:81]1[CH2:87][CH2:86][CH2:85][N:84]([C:48]2[CH:49]=[C:50]3[C:55](=[CH:56][CH:57]=2)[N:54]=[C:53]([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([Cl:64])[CH:59]=2)[N:52]([CH2:65][C:66](=[O:67])[NH:68][C:69]([CH3:72])([CH3:71])[CH3:70])[C:51]3=[O:73])[CH2:83][CH2:82]1)=[O:80])([CH3:77])([CH3:75])[CH3:76]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 59519057HCID 59519057, compound

Product 1

HCID 59519096HCID 59519096, compoundYield 46.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (5 mg, 0.009 mmol) and anhydrous toluene (0.5 mL) was heated in a microwave vial with stirring at 80° C. under an Argon atmosphere until a homogeneous milky solution was obtained (˜5 min). This solution was cooled to room temperature and palladium(II) acetate (2 mg, 0.006 mmol) was added. After stirring at room temperature for 2 min., 2-[6-bromo-2-(3-chlorophenyl)-4-oxo-4H-quinazolin-3-yl]-N-tert-butylacetamide (INTERMEDIATE VI.1) (67 mg, 0.15 mmol), tert-butyl-1-homopiperazinecarboxylate (35 μL, 0.18 mmol) and freshly ground cesium carbonate (68 mg, 0.21 mmol) were added to the red solution. Anhydrous dioxane (0.2 mL) was added to rinse down solid left on the side of the vial. The vial was capped and heated in a microwave at 120° C. for 40 min. The reaction mixture was diluted with DCM (3 mL), filtered and the filtrate concentrated in vacuo. This crude product was purified by preparative TLC on silica gel with hexane:EtOAc:CH2Cl2 (1:1:1, v/v) as eluent to give 4-[3-(tert-butylcarbamoylmethyl)-2-(3-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-6-yl]perhydro-1,4-diazepine-1-carboxylic acid tert-butyl ester (INTERMEDIATE VIII.1) (38.9 mg, 0.07 mmol, 46%) as a yellow solid.

Workup

  1. customwas obtained (˜5 min)
  2. temperatureThis solution was cooled to room temperature
  3. stirringAfter stirring at room temperature for 2 min.
  4. washto rinse down solid
  5. waitleft on the side of the vial
  6. customThe vial was capped
  7. temperatureheated in a microwave at 120° C. for 40 min
  8. additionThe reaction mixture was diluted with DCM (3 mL)
  9. filtrationfiltered
  10. concentrationthe filtrate concentrated in vacuo
  11. customThis crude product was purified by preparative TLC on silica gel with hexane:EtOAc:CH2Cl2 (1:1:1

Sources & evidence

ORD record
ord-720e0ebb9a8d44139376a7e021c74072
Source dataset
uspto-grants-2010_10
Patent number
US07820649B2

Reaction notes

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