Water → HCID 56643608, compound

HRID 1526685Notes

Reaction equation

HRID 1526685 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)S(O[C:23]1[CH:24]=[CH:25][C:26]2[N:32]3[C:33]([CH3:36])=[N:34][N:35]=[C:31]3[C@H:30]([CH2:37][C:38]([NH:40][CH2:41][CH3:42])=[O:39])[N:29]=[C:28]([C:43]3[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=3)[C:27]=2[CH:50]=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:49][C:46]1[CH:47]=[CH:48][C:43]([C:28]2[C:27]3[CH:50]=[C:23]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=4[CH3:10])[CH:24]=[CH:25][C:26]=3[N:32]3[C:33]([CH3:36])=[N:34][N:35]=[C:31]3[C@H:30]([CH2:37][C:38]([NH:40][CH2:41][CH3:42])=[O:39])[N:29]=2)=[CH:44][CH:45]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 86679715HCID 86679715, compound2×

Product 1

HCID 56643608HCID 56643608, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

o-Tolylboronic acid (30.1 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) and then at 120° C. for a further 30 min (microwave). Bis(triphenylphosphine)palladium(II) chloride (12.7 mg) was added and the reaction mixture was heated at 120° C. for 30 min (microwave). The reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml). The organic phase was separated and washed with water (10 ml) and brine (10 ml), dried and the solvent evaporated. The residue was chromatographed (0-5% methanol:DCM). The resulting mixture was repurified by MDAP (formate modifier) to give 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide as a white oil (16.8 mg). LCMS (formate): MH+ 484/486, RT 1.14 min

Workup

  1. temperaturethe reaction mixture was heated at 120° C. for 30 min (microwave)
  2. customThe reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml)
  3. customThe organic phase was separated
  4. washwashed with water (10 ml) and brine (10 ml)
  5. customdried
  6. customthe solvent evaporated
  7. customThe residue was chromatographed (0-5% methanol:DCM)
  8. customThe resulting mixture was repurified by MDAP (formate modifier)

Sources & evidence

ORD record
ord-f204ba2b555647cc9f15a193aef476de
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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