Cesium carbonate → HCID 67282815, compound

HRID 1910700Notes

Reaction equation

HRID 1910700 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:42]1[C:43]2[CH:73]=[C:72]([Cl:74])[CH:71]=[CH:70][C:44]=2[N:45]([CH2:61][C:62]2[CH:67]=[CH:66][C:65]([O:68][CH3:69])=[CH:64][CH:63]=2)[C:46](=[O:60])[CH:47]([CH2:49][C:50]2[CH:59]=[CH:58][C:57]3[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=3)[CH:51]=2)[N:48]=1.[O:75]1[C:79]2([CH2:84][CH2:83][NH:82][CH2:81][CH2:80]2)[O:78][CH2:77][CH2:76]1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:74][C:72]1[CH:71]=[CH:70][C:44]2[N:45]([CH2:61][C:62]3[CH:67]=[CH:66][C:65]([O:68][CH3:69])=[CH:64][CH:63]=3)[C:46](=[O:60])[CH:47]([CH2:49][C:50]3[CH:59]=[CH:58][C:57]4[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=4)[CH:51]=3)[N:48]=[C:42]([N:82]3[CH2:83][CH2:84][C:79]4([O:78][CH2:77][CH2:76][O:75]4)[CH2:80][CH2:81]3)[C:43]=2[CH:73]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67282421HCID 67282421, compound

Product 1

HCID 67282815HCID 67282815, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Palladium acetate (8 mg, 0.038 mmol), X-Phos (18 mg, 0.038 mmol), and cesium carbonate (270 mg, 0.83 mmol) were combined in anhydrous toluene (2 mL), and nitrogen bubbled through the solution for 5 minutes. A solution of 5,7-dichloro-1-(4-methoxybenzyl)-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (370 mg, 0.76 mmol) and 1,4-dioxa-8-azaspiro[4.5]decane (0.12 mL, 0.91 mmol) in toluene (2 mL) was added and then heated to 120° C. under a nitrogen blanket for 14 hours. The solution was cooled, diluted with ethyl acetate, washed with water, brine, dried with sodium sulfate, decanted, then concentrated in the presence of silica. Column chromatography eluting with a gradient of 10-70% ethyl acetate in hexanes provided 7-chloro-1-(4-methoxybenzyl)-3-(naphthalen-2-ylmethyl)-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one. (345 mg, 77% yield). ESI m/z measured 596.2321 [M+H]+. calculated 596.2316.

Workup

  1. customnitrogen bubbled through the solution for 5 minutes
  2. temperatureThe solution was cooled
  3. washwashed with water, brine
  4. dry with materialdried with sodium sulfate
  5. customdecanted
  6. concentrationconcentrated in the presence of silica
  7. washColumn chromatography eluting with a gradient of 10-70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4c8364e39cb64e22af15dc328e54652e
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

Loading…