Lithium Chloride → 6-(4-chlorophenyl)-1-methyl-8-(pyrimidin-2-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

HRID 1485417Notes

Reaction equation

HRID 1485417 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[CH2:9][CH2:8][N:7]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[C:6]=2[CH:23]=1.C([Sn](CCCC)(CCCC)[C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1)CCC.[Cl-].[Li+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([N:7]2[CH2:8][CH2:9][C:10]3=[N:14][N:13]=[C:12]([CH3:15])[N:11]3[C:5]3[CH:4]=[CH:3][C:2]([C:29]4[N:34]=[CH:33][CH:32]=[CH:31][N:30]=4)=[CH:23][C:6]2=3)=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 27632512-(Tributylstannyl)pyrimidineHCID 709789288-bromo-6-(4-chlorophenyl)-1-methyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine2×

Product 1

HCID 709793666-(4-chlorophenyl)-1-methyl-8-(pyrimidin-2-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepineYield 5.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 25 mL sealed-tube evacuated and brimmed with nitrogen, was charged with a mixture of 8-bromo-6-(4-chlorophenyl)-1-methyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (Compound 13; 40 mg, 0.10 mmol), 2-(tributylstannyl)pyrimidine (56.8 g, 0.15 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7.2 mg, 0.01 mmol), lithium chloride (6.5 mg, 0.15 mmol) and toluene (2 mL). The mixture was heated for 12 hours at 100° C. The mixture was concentrated in vacuo, partitioned with ethyl acetate (10 mL) and water (5 mL). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated to give a residue. The residue was purified by prep-HPLC (Phenomenex C18 (150 mm*21.2 mm*5 um), acetonitrile/water=1:100 (0.1% formic acid), flow rate: 30 mL/min) to yield 6-(4-chlorophenyl)-1-methyl-8-(pyrimidin-2-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine as a white solid (2 mg, 5%).

Workup

  1. customInto a 25 mL sealed-tube evacuated
  2. concentrationThe mixture was concentrated in vacuo
  3. custompartitioned with ethyl acetate (10 mL) and water (5 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto give a residue
  9. customThe residue was purified by prep-HPLC (Phenomenex C18 (150 mm*21.2 mm*5 um), acetonitrile/water=1:100 (0.1% formic acid), flow rate: 30 mL/min)

Sources & evidence

ORD record
ord-8e572b3ae34a481f89736e30505fdecc
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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