Dimethylacetamide → HCID 178502400, compound

HRID 1411372Notes

Reaction equation

HRID 1411372 reaction equation
[CH3:1][C:2]1([CH3:8])[CH2:4][C@@H:3]1[C:5](O)=[O:6].CN(C(O[N:17]1N=N[C:19]2[CH:20]=[CH:21][CH:22]=[N:23][C:18]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:33][C:34]([N:36]([CH3:38])C)=O.O[C:40]([C:42](F)(F)F)=O.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[CH3:60][O:61][C:62](=[O:113])[NH:63][C@H:64]([C:68]([N:70]1[CH2:74][CH2:73][CH2:72][C@H:71]1[C:75]1[NH:76][CH:77]=[C:78]([C:80]2[CH:85]=[CH:84][C:83]([C:86]3[CH:91]=[C:90]([F:92])[C:89]([NH:93][C:94](C4C=NC(N5CCNC[C@H]5C)=CC=4)=[O:95])=[CH:88][C:87]=3[C:109]([F:112])([F:111])[F:110])=[CH:82][CH:81]=2)[N:79]=1)=[O:69])[CH:65]([CH3:67])[CH3:66].C(N(CC)C(C)C)(C)C>>[CH3:60][O:61][C:62](=[O:113])[NH:63][C@H:64]([C:68]([N:70]1[CH2:74][CH2:73][CH2:72][C@H:71]1[C:75]1[NH:76][CH:77]=[C:78]([C:80]2[CH:85]=[CH:84][C:83]([C:86]3[CH:91]=[C:90]([F:92])[C:89]([NH:93][C:94]([C:21]4[CH:22]=[N:23][C:18]([N:17]5[CH2:33][CH2:34][N:36]([C:5]([C@H:3]6[CH2:4][C:2]6([CH3:8])[CH3:1])=[O:6])[CH2:38][C@H:40]5[CH3:42])=[CH:19][CH:20]=4)=[O:95])=[CH:88][C:87]=3[C:109]([F:111])([F:112])[F:110])=[CH:82][CH:81]=2)[N:79]=1)=[O:69])[CH:65]([CH3:66])[CH3:67]

Participants

6

Reactant 5

HCID 31374DimethylacetamideHCID 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 178502399HCID 178502399, compound

Product 1

HCID 178502400HCID 178502400, compoundYield 31.5%

Procedure

A mixture of (S)-(+)-2,2-dimethylcyclopropane carboxylic acid (2.09 mg, 0.018 mmol) and HATU (8.35 mg, 0.022 mmol) was stirred in DMA (1.0 mL, 11 mmol) for 10 min. and then ((S)-1-{(S)-2-[4-(5′-fluoro-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 tri-TFA (20.0 mg, 0.018 mmol, Preparation 41) and N,N-diisopropylethylamine (15.94 uL, 0.091 mmol) were added. The reaction mixture was stirred at RT overnight, concentrated by rotary evaporation, dissolved in 1:1 acetic acid:water (1.5 mL), filtered, and purified by preparative HPLC to provide the di-TFA salt of the title compound (4.8 mg). (m/z): [M+H]+ calcd for C44H50F4N8O5 847.38 found 847.4.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. dissolutiondissolved in 1:1 acetic acid
  3. filtrationwater (1.5 mL), filtered
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-0a80306525364af69642ae0473fdc809
Source dataset
uspto-grants-2014_12
Patent number
US08921372B2

Reaction notes

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