Diisopropylethylamine → HCID 178502393, compound

HRID 1500531Notes

Reaction equation

HRID 1500531 reaction equation
[CH3:1][O:2][C:3](=[O:39])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][C:28]=3[O:34][C:35]([F:38])([F:37])[F:36])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].Cl[C:41](OC1C=CC([N+]([O-])=O)=CC=1)=[O:42].Cl.Cl.[CH:55]1([C:58]([N:60]2[CH2:65][CH2:64][CH:63]([N:66]3[CH2:71][CH2:70][NH:69][CH2:68][C@@H:67]3[CH3:72])[CH2:62][CH2:61]2)=[O:59])[CH2:57][CH2:56]1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:1][O:2][C:3](=[O:39])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:41]([N:69]4[CH2:70][CH2:71][N:66]([CH:63]5[CH2:64][CH2:65][N:60]([C:58]([CH:55]6[CH2:56][CH2:57]6)=[O:59])[CH2:61][CH2:62]5)[C@@H:67]([CH3:72])[CH2:68]4)=[O:42])=[CH:29][C:28]=3[O:34][C:35]([F:38])([F:36])[F:37])=[CH:25][CH:26]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 131734277cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanone 2 HClHCID 178502381HCID 178502381, compound

Product 1

HCID 178502393HCID 178502393, compoundYield 20.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of ((S)-1-{(S)-2-[4-(4′-amino-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (20 mg, 0.04 mmol) and p-nitrophenyl chloroformate (8.9 mg, 0.04 mmol) in DMA (5 mL) was stirred at RT for 30 min and then cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanone 2 HCl (18 mg, 0.06 mmol; Preparation 6) was added followed by DIPEA (32 μL, 0.18 mmol). The reaction mixture was stirred at RT for 1 h, concentrated, dissolved in 1:1 acetic acid:water (1.5 mL), and purified by reverse phase HPLC to provide the di-TFA salt of the title product (6.8 mg, 20% yield) (m/z): [M+H]+ calcd for C42H53F3N8O6 823.40 found 823.6.

Workup

  1. stirringThe reaction mixture was stirred at RT for 1 h
  2. concentrationconcentrated
  3. dissolutiondissolved in 1:1 acetic acid
  4. customwater (1.5 mL), and purified by reverse phase HPLC

Sources & evidence

ORD record
ord-cfa0275c5bae47b69a9105603c61e27e
Source dataset
uspto-grants-2015_12
Patent number
US09206159B2

Reaction notes

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