Triethylamine → HCID 178480679, compound

HRID 467587

Reaction equation

HRID 467587 reaction equation
[C:1](OC(OC(C)(C)C)=O)(OC(C)(C)C)=[O:2].[Cl:16][C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:18]=1[NH2:19].Cl.Cl.C(OC([N:32]1[C:36]([NH:37][C:38](=[O:52])[C:39]2[CH:44]=[CH:43][C:42]([N:45]3[CH2:50][CH2:49][N:48]([CH3:51])[CH2:47][CH2:46]3)=[CH:41][CH:40]=2)=[C:35]2[CH2:53][NH:54][C:55]([CH3:57])([CH3:56])[C:34]2=[N:33]1)=O)C.C(N(CC)CC)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:16][C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:18]=1[NH:19][C:1]([N:54]1[CH2:53][C:35]2[C:34](=[N:33][NH:32][C:36]=2[NH:37][C:38](=[O:52])[C:39]2[CH:44]=[CH:43][C:42]([N:45]3[CH2:50][CH2:49][N:48]([CH3:51])[CH2:47][CH2:46]3)=[CH:41][CH:40]=2)[C:55]1([CH3:56])[CH3:57])=[O:2]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 90495Di-tert-butyl dicarbonateHCID 27342052-Chloro-6-fluoroanilineHCID 672375746,6-Dimethyl-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester dihydrochloride

Product 1

HCID 178480679HCID 178480679, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of di-tert-butyl dicarbonate (101 mg, 0.46 mmol, 1.1 eq) in DCM (2 mL) was added 2-chloro-6-fluoroaniline (61 mg, 0.42 mmol, 1 eq) and N,N-dimethylpyridin-4-amine (51 mg, 0.42 mmol, 1 eq). After 1 hour of agitation at room temperature, 6,6-Dimethyl-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4Hpyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester dihydrochloride (189 mg, 0.38 mmol, 0.9 eq), triethylamine (0.23 mL, 1.68 mmol, 4 eq) and an additional 2 mL of DCM (4 mL total). The cocktail was placed in a Personal Chemistry, Smith Creator microwave reaction station and the vial contents were irradiated at 125° C. for 10 minutes with application of continuous, simultaneous cooling. After the 10 minutes of heating time had elapsed, the solution was washed twice with water. The organic phase was collected and the solvent was removed in vacuo. The residue was dissolved in methanol (3 mL), treated with triethylamine (0.3 mL, 2.2 mmol, 5 eq) and agitated for 6 hours at 50° C. After evaporation of the solvent, the solid was purified by preparative HPLC to afford 0.012 g of the title compound in 5% overall yield.

Workup

  1. customthe vial contents were irradiated at 125° C. for 10 minutes with application of continuous, simultaneous cooling
  2. temperatureAfter the 10 minutes of heating time
  3. washthe solution was washed twice with water
  4. customThe organic phase was collected
  5. customthe solvent was removed in vacuo
  6. dissolutionThe residue was dissolved in methanol (3 mL)
  7. customAfter evaporation of the solvent
  8. customthe solid was purified by preparative HPLC

Sources & evidence

ORD record
ord-151144188a5e4adaaa0764b86c3dce99
Source dataset
uspto-grants-2014_01
Patent number
US08623876B2

Linked notes

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