Water → HCID 56643604, compound

HRID 1526681Notes

Reaction equation

HRID 1526681 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[N:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:29]3[CH:30]=[C:31](OS(C(F)(F)F)(=O)=O)[CH:32]=[CH:33][C:28]=3[N:27]3[C:42]([CH3:45])=[N:43][N:44]=[C:26]3[C@H:25]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[N:24]=2)=[CH:19][CH:18]=1.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:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:29]3[CH:30]=[C:31]([C:10]4[CH:11]=[CH:12][N:7]=[CH:8][CH:9]=4)[CH:32]=[CH:33][C:28]=3[N:27]3[C:42]([CH3:45])=[N:43][N:44]=[C:26]3[C@H:25]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[N:24]=2)=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 86679711HCID 86679711, compound

Product 1

HCID 56643604HCID 56643604, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

Sodium carbonate (66.3 mg), 4-pyridinylboronic acid (22.5 mg) and bis(triphenylphosphine)palladium(II) chloride (19.1 mg) were added to a 2-5 ml microwave vial. A solution of ethyl ((4S)-6-(4-chlorophenyl)-1-methyl-8-{[(trifluoromethyl)sulfonyl]oxy}-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)acetate (for a preparation see intermediate 2) (147.5 mg) in DME (3 ml) and water (1 ml) was added to the microwave vial. The reaction mixture was heated at 120° C. for 90 min (microwave). Ethyl acetate (2 ml) was added and the water layer was separated and acidified with glacial acetic acid. The aqueous was extracted with ethyl acetate (3×5 ml), the organic fractions dried and the solvent evaporated. The residue was chromatographed (0-10% methanol:DCM) and then further purified by MDAP (formate modifier) to give ethyl [(4S)-6-(4-chlorophenyl)-1-methyl-8-(4-pyridinyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetate as a white solid (5.5 mg).

Workup

  1. customthe water layer was separated
  2. extractionThe aqueous was extracted with ethyl acetate (3×5 ml)
  3. customthe organic fractions dried
  4. customthe solvent evaporated
  5. customThe residue was chromatographed (0-10% methanol:DCM)
  6. customfurther purified by MDAP (formate modifier)

Sources & evidence

ORD record
ord-d00f7c261c4f499f9a837e86a8a3bd0e
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

Loading…