Diisopropylethylamine → HCID 178502376, compound

HRID 1411373Notes

Reaction equation

HRID 1411373 reaction equation
[CH3:1][C:2]1([CH3:8])[CH2:4][C@@H:3]1[C:5](O)=[O:6].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:33][O:34][C:35](=[O:86])[NH:36][C@H:37]([C:41]([N:43]1[CH2:47][CH2:46][CH2:45][C@H:44]1[C:48]1[NH:49][CH:50]=[C:51]([C:53]2[CH:58]=[CH:57][C:56]([C:59]3[CH:64]=[C:63]([Cl:65])[C:62]([NH:66][C:67]([C:69]4[CH:70]=[N:71][C:72]([N:75]5[CH2:80][CH2:79][NH:78][CH2:77][C@H:76]5[CH3:81])=[CH:73][CH:74]=4)=[O:68])=[CH:61][C:60]=3[C:82]([F:85])([F:84])[F:83])=[CH:55][CH:54]=2)[N:52]=1)=[O:42])[CH:38]([CH3:40])[CH3:39].C(N(CC)C(C)C)(C)C>CC(N(C)C)=O>[CH3:33][O:34][C:35](=[O:86])[NH:36][C@H:37]([C:41]([N:43]1[CH2:47][CH2:46][CH2:45][C@H:44]1[C:48]1[NH:49][CH:50]=[C:51]([C:53]2[CH:58]=[CH:57][C:56]([C:59]3[CH:64]=[C:63]([Cl:65])[C:62]([NH:66][C:67]([C:69]4[CH:70]=[N:71][C:72]([N:75]5[CH2:80][CH2:79][N:78]([C:5]([C@H:3]6[CH2:4][C:2]6([CH3:8])[CH3:1])=[O:6])[CH2:77][C@H:76]5[CH3:81])=[CH:73][CH:74]=4)=[O:68])=[CH:61][C:60]=3[C:82]([F:84])([F:85])[F:83])=[CH:55][CH:54]=2)[N:52]=1)=[O:42])[CH:38]([CH3:40])[CH3:39]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10192561(1S)-2,2-Dimethylcyclopropane-1-carboxylic acidHCID 178502375HCID 178502375, compound

Product 1

HCID 178502376HCID 178502376, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of 0.5 M (S)-(+)-2,2-dimethylcyclopropane carboxylic acid in DMA (28.9 μL, 0.015 mmol;). and HATU (8.25 mg, 0.022 mmol) dissolved in DMA (0.5 mL), was added ((S)-1-{(S)-2-[4-(5′-Chloro-4′-{[6-((R)-2-methyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2′-trifluoromethyl-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester 3 TFA (16 mg, 0.014 mmol; Preparation 53) and N,N-diisopropylethylamine (25.2 uL, 0.15 mmol) and the reaction mixture was stirred at RT overnight, concentrated, dissolved in 1:1 acetic acid:water (1.5 mL) and purified by reverse phase HPLC to provide the title compound (8.6 mg) as the di-TFA salt. (m/z): [M+H]+ calcd for C11H50ClF3N8O5 863.35 found 863.4.

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in 1:1 acetic acid
  3. customwater (1.5 mL) and purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d93dd971104c4f349dd4b433df8240c7
Source dataset
uspto-grants-2014_12
Patent number
US08921372B2

Reaction notes

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