Water → HCID 56643605, compound

HRID 1526683Notes

Reaction equation

HRID 1526683 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[NH:7]1[C:11](B(O)O)=[CH:10][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.O>COCCOC.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.C(OCC)(=O)C>[Cl:47][C:44]1[CH:43]=[CH:42][C:41]([C:26]2[C:25]3[CH:48]=[C:21]([C:11]4[NH:7][N:8]=[CH:9][CH:10]=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 962WaterHCID 10340Sodium CarbonateHCID 112519791H-Pyrazole-5-boronic acidHCID 86679715HCID 86679715, compound

Product 1

HCID 56643605HCID 56643605, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Sodium carbonate (43.0 mg), 1H-pyrazole-5-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 (for a preparation see intermediate 3) (100 mg) 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 phase was dried and the solvent evaporated. The residue was chromatographed (0-5% methanol:DCM) and the product further purified by MDAP (formate modifier). The resulting gum was loaded on a 1 g SCX-2 column and washed with ammonia in methanol (2M) to give 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-5-yl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide as a brown oil (15.6 mg).

Workup

  1. customthe water layer was separated
  2. customThe organic phase was dried
  3. customthe solvent evaporated
  4. customThe residue was chromatographed (0-5% methanol:DCM)
  5. customthe product further purified by MDAP (formate modifier)
  6. washwashed with ammonia in methanol (2M)

Sources & evidence

ORD record
ord-fab2cf4edc1648caa17889c261ee35d6
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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