Water → HCID 56643606, compound

HRID 1526682Notes

Reaction equation

HRID 1526682 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)S(O[C:24]1[CH:25]=[CH:26][C:27]2[N:33]3[C:34]([CH3:37])=[N:35][N:36]=[C:32]3[C@H:31]([CH2:38][C:39]([NH:41][CH2:42][CH3:43])=[O:40])[N:30]=[C:29]([C:44]3[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=3)[C:28]=2[CH:51]=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:50][C:47]1[CH:46]=[CH:45][C:44]([C:29]2[C:28]3[CH:51]=[C:24]([C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH:25]=[CH:26][C:27]=3[N:33]3[C:34]([CH3:37])=[N:35][N:36]=[C:32]3[C@H:31]([CH2:38][C:39]([NH:41][CH2:42][CH3:43])=[O:40])[N:30]=2)=[CH:49][CH:48]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 86679715HCID 86679715, compound

Product 1

HCID 56643606HCID 56643606, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

4-Methoxybenzeneboronic acid (50.5 mg), sodium carbonate (64.5 mg) and bis(triphenylphosphine)palladium(II) chloride (19.4 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) (150 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 was evaporated. The residue was chromatographed (0-5% methanol:DCM) to give 2-{(4S)-6-(4-chlorophenyl)-1-methyl-8-[4-(methyloxy)phenyl]-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl}-N-ethylacetamide as a light brown solid (84 mg). LCMS (formate): MH+ 500/502, RT 1.08 min

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 was evaporated
  6. customThe residue was chromatographed (0-5% methanol:DCM)

Sources & evidence

ORD record
ord-3770f455509b4472a364a2e54874ac98
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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