1,2-Dichloroethane → HCID 178502392, compound

HRID 1776054Notes

Reaction equation

HRID 1776054 reaction equation
[CH3:1][C:2]1([CH3:23])[CH2:4][C@@H:3]1[C:5]([N:7]1[CH2:12]C[N:10]([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][N:14]=2)[C@H:9](C)[CH2:8]1)=[O:6].[CH2:24](Cl)[CH2:25]Cl.C1C=NC2N(O)N=NC=2C=1.CC(N(C)C)=O.[CH3:44][O:45][C:46](=[O:79])[NH:47][C@H:48]([C:52]([N:54]1[CH2:58][CH2:57][CH2:56][C@H:55]1[C:59]1[NH:60][CH:61]=[C:62]([C:64]2[CH:69]=[CH:68][C:67]([C:70]3[CH:75]=[CH:74][C:73]([NH2:76])=[CH:72][C:71]=3[F:77])=[C:66]([F:78])[CH:65]=2)[N:63]=1)=[O:53])[CH:49]([CH3:51])[CH3:50].C(N(CC)C(C)C)(C)C>>[CH3:44][O:45][C:46](=[O:79])[NH:47][C@H:48]([C:52]([N:54]1[CH2:58][CH2:57][CH2:56][C@H:55]1[C:59]1[NH:60][CH:61]=[C:62]([C:64]2[CH:69]=[CH:68][C:67]([C:70]3[CH:75]=[CH:74][C:73]([NH:76][C:17]([C:16]4[CH:15]=[N:14][C:13]([N:10]5[CH2:9][CH2:8][N:7]([C:5]([C@H:3]6[CH2:4][C:2]6([CH3:1])[CH3:23])=[O:6])[CH2:12][C@H:24]5[CH3:25])=[CH:21][CH:20]=4)=[O:19])=[CH:72][C:71]=3[F:77])=[C:66]([F:78])[CH:65]=2)[N:63]=1)=[O:53])[CH:49]([CH3:51])[CH3:50]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 674951146-[(R)-4-((S)-2,2-dimethyl-cyclopropanecarbonyl)-2-methyl-piperazin-1-yl]-nicotinic acidHCID 178502380HCID 178502380, compound

Product 1

HCID 178502392HCID 178502392, compoundYield 42.7%

Procedure

To a solution of 6-[(R)-4-((S)-2,2-dimethyl-cyclopropanecarbonyl)-2-methyl-piperazin-1-yl]-nicotinic acid (6.4 mg, 0.020 mmol; Preparation 36) was added EDC (5.8 mg, 0.030 mmol) and HOAt (4.2 mg, 0.030 mmol) in DMA (0.5 mL, 5 mmol). The reaction mixture was stirred at RT for 30 min and then ((S)-1-{(S)-2-[4-(4′-amino-2,2′-difluoro-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (10 mg, 0.02 mmol; Preparation 38-B) and N,N-diisopropylethylamine (18 uL, 0.10 mmol) were added and the reaction mixture was stirred at RT overnight. The reaction mixture was concentrated by rotary evaporation, 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 compound (6.8 mg). (m/z): [M+H]+ calcd for C43H50F2N8O5 797.39 found 797.4.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. concentrationThe reaction mixture was concentrated by rotary evaporation
  3. dissolutiondissolved in 1:1 acetic acid
  4. customwater (1.5 mL) and purified by reverse phase HPLC

Sources & evidence

ORD record
ord-cdfdd410a1774b29bd413ea2f0372779
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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