Dimethylformamide → HCID 178502388, compound

HRID 1411366Notes

Reaction equation

HRID 1411366 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.C(OC([N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24]C(C(O)=O)=[CH:22][N:21]=2)[CH2:16][CH2:15]1)=O)(C)(C)C.ClCCl.CN(C)C=O.C(N(CC)C(C)C)(C)C.[CH3:46][O:47][C:48](=[O:79])[NH:49][C@H:50]([C:54]([N:56]1[CH2:60][CH2:59][CH2:58][C@H:57]1[C:61]1[NH:62][CH:63]=[C:64]([C:66]2[CH:71]=[CH:70][C:69]([C:72]3[CH:77]=[CH:76][C:75]([NH2:78])=[CH:74][CH:73]=3)=[CH:68][CH:67]=2)[N:65]=1)=[O:55])[CH:51]([CH3:53])[CH3:52].O1CCOCC1>Cl>[CH3:46][O:47][C:48](=[O:79])[NH:49][C@H:50]([C:54]([N:56]1[CH2:60][CH2:59][CH2:58][C@H:57]1[C:61]1[NH:62][CH:63]=[C:64]([C:66]2[CH:67]=[CH:68][C:69]([C:72]3[CH:73]=[CH:74][C:75]([NH:78][C:1]([C:2]4[CH:22]=[N:21][C:20]([N:17]5[CH2:16][CH2:15][NH:14][CH2:19][CH2:18]5)=[CH:25][CH:24]=4)=[O:5])=[CH:76][CH:77]=3)=[CH:70][CH:71]=2)[N:65]=1)=[O:55])[CH:51]([CH3:53])[CH3:52]

Participants

9

Reactant 7

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 312751,4-DioxaneHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 27718236-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acidHCID 178502377HCID 178502377, compound

Product 1

HCID 178502388HCID 178502388, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

Oxalyl chloride (44.0 uL, 0.520 mmol) was added to a solution of 4-(5-carboxy-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (70.3 mg, 0.229 mmol) in dichloromethane (6.67 mL, 104 mmol) and N,N-dimethylformamide (2.01 uL, 0.026 mmol) The reaction mixture was stirred at room temperature for 20 min and then N,N-diisopropylethylamine (0.181 mL, 1.04 mmol) was added followed by ((S)-1-{(S)-2-[4-(4′-amino-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (100.0 mg, 0.217 mmol). The reaction mixture was stirred for 2 h at room temperature, then dried by rotary evaporation. The crude material was dissolved in dichloromethane (1 mL) and then washed with saturated aqueous sodium bicarbonate (1 mL). The organic layer was concentrated, dissolved in 4.0 M hydrogen chloride in 1,4-dioxane (6.7 mL, 27 mmol) and stirred for 1 h at room temperature until completely deprotected. The reaction mixture was concentrated and used directly in the next step.

Workup

  1. stirringThe reaction mixture was stirred for 2 h at room temperature
  2. customdried by rotary evaporation
  3. dissolutionThe crude material was dissolved in dichloromethane (1 mL)
  4. washwashed with saturated aqueous sodium bicarbonate (1 mL)
  5. concentrationThe organic layer was concentrated
  6. stirringstirred for 1 h at room temperature
  7. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-096b887c47cd46a49ba9edbd2db2d89f
Source dataset
uspto-grants-2014_12
Patent number
US08921372B2

Reaction notes

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