Water → HCID 56643809, compound

HRID 1526686Notes

Reaction equation

HRID 1526686 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)S(O[C:22]1[CH:23]=[CH:24][C:25]2[N:31]3[C:32]([CH3:35])=[N:33][N:34]=[C:30]3[C@H:29]([CH2:36][C:37]([NH:39][CH2:40][CH3:41])=[O:38])[N:28]=[C:27]([C:42]3[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=3)[C:26]=2[CH:49]=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>[Cl:48][C:45]1[CH:44]=[CH:43][C:42]([C:27]2[C:26]3[CH:49]=[C:22]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH:23]=[CH:24][C:25]=3[N:31]3[C:32]([CH3:35])=[N:33][N:34]=[C:30]3[C@H:29]([CH2:36][C:37]([NH:39][CH2:40][CH3:41])=[O:38])[N:28]=2)=[CH:47][CH:46]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 86679715HCID 86679715, compound2×

Product 1

HCID 56643809HCID 56643809, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

3-Pyridinylboronic acid (27.2 mg), sodium carbonate (43.0 mg) and bis(triphenylphosphine)palladium(II) chloride (12.95 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 and the reaction mixture was heated at 120° C. for 20 min (microwave). The reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml). The organic phase was separated, washed with water (10 ml) and brine (10 ml). The organic phase was dried and the solvent evaporated. The residue was chromatographed (0-10% methanol:DCM) product was further purified by MDAP (formate modifier) to give 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(3-pyridinyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide as a white oil (11.9 mg).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml)
  2. customThe organic phase was separated
  3. washwashed with water (10 ml) and brine (10 ml)
  4. customThe organic phase was dried
  5. customthe solvent evaporated
  6. customThe residue was chromatographed (0-10% methanol:DCM) product
  7. customwas further purified by MDAP (formate modifier)

Sources & evidence

ORD record
ord-1ab9053371da4f339a828d1cc0aa778a
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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