1-Methylpiperazine → HCID 178481079, compound

HRID 448272Notes

Reaction equation

HRID 448272 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.Cl.[F:14][C:15]1[CH:38]=[CH:37][C:18]([C:19]([NH:21][C:22]2[N:26](C(OCC)=O)[N:25]=[C:24]3[C:32]([CH3:36])([CH3:35])[NH:33][CH2:34][C:23]=23)=[O:20])=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.[CH3:48][N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>C(Cl)Cl.CCOC(C)=O.CCCCCC>[CH3:36][C:32]1([CH3:35])[C:24]2=[N:25][NH:26][C:22]([NH:21][C:19](=[O:20])[C:18]3[CH:17]=[CH:16][C:15]([F:14])=[CH:38][CH:37]=3)=[C:23]2[CH2:34][N:33]1[C:5]([N:52]1[CH2:53][CH2:54][N:49]([CH3:48])[CH2:50][CH2:51]1)=[O:11]

Participants

7

Reactant 4

HCID 531671-MethylpiperazineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 68649464HCID 68649464, compound

Product 1

HCID 178481079HCID 178481079, compoundYield 112.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 21226206Ethyl acetate hexaneSolvent2×

Procedure

To a solution of triphosgene (195 mg, 0.65 mmol, 0.56 eq) in DCM (15 ml) was added a solution of ethyl 3-[(4-fluorobenzoyl)amino]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-2(4H)-carboxylate hydrochloride (442 mg, 1.15 mmol) in DCM (30 ml) followed by N,N-diisopropylethylamine (760 μl, 4.31 mmol, 3.75 eq). After 3 hours, a solution of N-methylpiperazine (195 μl, 1.72 mmol, 1.5 eq) and diisopropylethylamine (300 μl, 1.72 mmol, 1.5 eq) in DCM (8 ml) was added. The reaction was stirred overnight at room temperature (TLC:CH2Cl2/MeOH 90/10). The solution was washed with brine, the organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in methanol (16 ml), treated with TEA (1.6 ml, 11.5 mmol, 10 eq) and stirred overnight at room temperature. (TLC: CH2Cl2/MeOH 90/10). After evaporation, the solid was purified by flash chromatography (eluent: CH2Cl2/MeOH 90/10). The solid was treated with diisopropylether and filtered to afford 0.294 g of the title compound in 64% yield.

Workup

  1. washThe solution was washed with brine
  2. dry with materialthe organic phase was dried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in methanol (16 ml)
  5. customAfter evaporation
  6. customthe solid was purified by flash chromatography (eluent: CH2Cl2/MeOH 90/10)
  7. additionThe solid was treated with diisopropylether
  8. filtrationfiltered

Sources & evidence

ORD record
ord-234b9e540c00419d8f67610c5d1442c2
Source dataset
uspto-grants-2013_07
Patent number
US08481585B2

Reaction notes

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