Ethyl Acetate → HCID 56643607, compound

HRID 1526684Notes

Reaction equation

HRID 1526684 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[NH:7]1[CH:11]=[C:10](B(O)O)[CH:9]=[N:8]1.FC(F)(F)S(O[C:21]1[CH:22]=[CH:23][C:24]2[N:30]3[C:31]([CH3:34])=[N:32][N:33]=[C:29]3[C@H:28]([CH2:35][C:36]([NH:38][CH2:39][CH3:40])=[O:37])[N:27]=[C:26]([C:41]3[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=3)[C:25]=2[CH:48]=1)(=O)=O.C(OCC)(=O)C>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:47][C:44]1[CH:43]=[CH:42][C:41]([C:26]2[C:25]3[CH:48]=[C:21]([C:10]4[CH:9]=[N:8][NH:7][CH:11]=4)[CH:22]=[CH:23][C:24]=3[N:30]3[C:31]([CH3:34])=[N:32][N:33]=[C:29]3[C@H:28]([CH2:35][C:36]([NH:38][CH2:39][CH3:40])=[O:37])[N:27]=2)=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 177502781H-Pyrazole-4-boronic acidHCID 86679715HCID 86679715, compound2×

Product 1

HCID 56643607HCID 56643607, compoundYield 7.2%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

Sodium carbonate (43.0 mg), 1H-pyrazole-4-boronic acid (24.8 mg) and bis(triphenylphosphine)palladium(II) chloride (13.0 mg) were added to a 2-5 ml microwave vial. A solution of (4S)-6-(4-chlorophenyl)-4-[2-(ethylamino)-2-oxoethyl]-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-8-yl trifluoromethanesulfonate (100 mg, intermediate 3) in DME (3 ml) and water (1 ml) was added. The reaction mixture was heated at 120° C. for 30 min (microwave). Ethyl acetate (2 ml) was added and the water layer was separated. The organic layer was dried and the solvent evaporated. The residue was purified by MDAP (formate modifier). The product was loaded on a 1 g SCX-2 column in methanol and eluted with ammonia in methanol (2M) to give 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-4-yl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide as a white oil (6.1 mg).

Workup

  1. customthe water layer was separated
  2. customThe organic layer was dried
  3. customthe solvent evaporated
  4. customThe residue was purified by MDAP (formate modifier)
  5. washeluted with ammonia in methanol (2M)

Sources & evidence

ORD record
ord-4c959dfbbb0a49069be8e8b3030827b9
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

Loading…