Diisopropylethylamine → HCID 178480346, compound

HRID 1042390Notes

Reaction equation

HRID 1042390 reaction equation
Cl.[F:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([NH:9][C:10]2[C:11]3[CH2:22][NH:21][C:20]([CH3:24])([CH3:23])[C:12]=3[N:13](C(OCC)=O)[N:14]=2)=[O:8])=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[CH3:59][N:60]1[CH2:65][CH2:64][CH:63]([C:66](O)=[O:67])[CH2:62][CH2:61]1.C(Cl)Cl.CO.[NH4+].[OH-]>ClCCl.CCOC(C)=O.CCCCCC>[CH3:23][C:20]1([CH3:24])[C:12]2=[N:13][NH:14][C:10]([NH:9][C:7](=[O:8])[C:6]3[CH:5]=[CH:4][C:3]([F:2])=[CH:26][CH:25]=3)=[C:11]2[CH2:22][N:21]1[C:66]([CH:63]1[CH2:64][CH2:65][N:60]([CH3:59])[CH2:61][CH2:62]1)=[O:67]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27600434-Piperidinecarboxylic acid, 1-methyl-, hydrochloride (1:1)HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 68649268Ethyl 3-[(4-fluorobenzoyl)amino]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate hydrochloride

Product 1

HCID 178480346HCID 178480346, compoundYield 69.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Ethyl 3-[(4-fluorobenzoyl)amino]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate hydrochloride (0.5 g, 1.3 mmol), in dichloromethane (25 ml), was treated with N,N-diisopropylethylamine (1.13 ml, 6.5 mmol, 5 eq) and TBTU (0.542 g, 1.69 mmol, 1.3 eq), at room temperature for 1 hour, and then 1-methyl-piperidine-4-carboxylic acid hydrochloride (0.29 g, 1.61 mmol, 1.2 eq) was added. The reaction was stirred overnight (TLC: CH2Cl2/MeOH 90/10). The solution was washed with saturated sodium hydrogencarbonate aqueous solution and brine, the organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in methanol (16 ml), treated with TEA (2 ml, 14.3 mmol, 11 eq) and stirred overnight at room temperature. (TLC: CH2Cl2/MeOH/NH4OH 90/10/1). After evaporation, the solid was purified by flash chromatography (eluent: CH2Cl2/MeOH/NH4OH 90/10/2). The solid was treated with diisopropylether and filtered to afford 0.36 g of the title compound in 69% yield.

Workup

  1. washThe solution was washed with saturated sodium hydrogencarbonate aqueous solution and 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/NH4OH 90/10/2)
  7. additionThe solid was treated with diisopropylether
  8. filtrationfiltered

Sources & evidence

ORD record
ord-7460c87662d24c8abcfb3d1a15f3e46e
Source dataset
uspto-grants-2013_10
Patent number
US08557845B2

Reaction notes

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