Water → HCID 68003876, compound

HRID 1526676Notes

Reaction equation

HRID 1526676 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[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]CC)=[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:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=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]([OH:49])=[O:48])[N:24]=2)=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 86679711HCID 86679711, compound

Product 1

HCID 68003876HCID 68003876, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

Sodium carbonate (35.8 mg), phenylboronic acid (22.5 mg) and bis(triphenylphosphine)palladium(II) chloride (10.8 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) (83.4 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 water layer was extracted with ethyl acetate (3×5 ml) and the organic layer was dried and the solvent evaporated. The residue was chromatographed (0-10% methanol:DCM) to give [(4S)-6-(4-chlorophenyl)-1-methyl-8-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid as a white oil (30.1 mg), which was used without further purification in the subsequent reaction. LCMS (formate): MH+ 443/445, RT 1.09 min

Workup

  1. customthe water layer was separated
  2. extractionThe water layer was extracted with ethyl acetate (3×5 ml)
  3. customthe organic layer was dried
  4. customthe solvent evaporated
  5. customThe residue was chromatographed (0-10% methanol:DCM)

Sources & evidence

ORD record
ord-35403278e7f74774b924f06689dacad2
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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