Dimethylacetamide → HCID 178502391, compound

HRID 1776053Notes

Reaction equation

HRID 1776053 reaction equation
[CH3:1][C:2]1([CH3:23])[CH2:4][C@@H:3]1[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][N:14]=2)[C@H:9]([CH3:22])[CH2:8]1)=[O:6].CN(C(O[N:32]1N=N[C:34]2[CH:35]=[CH:36][C:37](=[CH:39][C:33]1=2)[Cl:38])=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.CC(N(C)C)=O.[CH3:64][O:65][C:66](=[O:98])[NH:67][C@H:68]([C:72]([N:74]1[CH2:78][CH2:77][CH2:76][C@H:75]1[C:79]1[NH:80][CH:81]=[C:82]([C:84]2[CH:89]=[CH:88][C:87](C3C=CC(N)=CC=3Cl)=[CH:86][CH:85]=2)[N:83]=1)=[O:73])[CH:69]([CH3:71])[CH3:70]>O.C(OCC)(=O)C>[CH3:64][O:65][C:66](=[O:98])[NH:67][C@H:68]([C:72]([N:74]1[CH2:78][CH2:77][CH2:76][C@H:75]1[C:79]1[NH:80][CH:81]=[C:82]([C:84]2[CH:85]=[CH:86][C:87]([C:36]3[CH:35]=[CH:34][C:33]([NH:32][C:17]([C:16]4[CH:15]=[N:14][C:13]([N:10]5[CH2:11][CH2:12][N:7]([C:5]([C@H:3]6[CH2:4][C:2]6([CH3:1])[CH3:23])=[O:6])[CH2:8][C@H:9]5[CH3:22])=[CH:21][CH:20]=4)=[O:18])=[CH:39][C:37]=3[Cl:38])=[CH:88][CH:89]=2)[N:83]=1)=[O:73])[CH:69]([CH3:71])[CH3:70]

Participants

8

Reactant 5

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate2×HCID 674951146-[(R)-4-((S)-2,2-dimethyl-cyclopropanecarbonyl)-2-methyl-piperazin-1-yl]-nicotinic acidHCID 178502379HCID 178502379, compound

Product 1

HCID 178502391HCID 178502391, compoundYield 11.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 6-[(R)-4-((S)-2,2-dimethyl-cyclopropanecarbonyl)-2-methyl-piperazin-1-yl]-nicotinic acid (4.54 mg, 0.014 mmol; Preparation 36), HCTU (8.0 mg, 0.019 mmol), N,N-diisopropylethylamine (0.013 mL, 0.072 mmol), and DMA (0.2 mL, 2 mmol) was stirred for 30 min at 50° C. and then ((S)-1-{(S)-2-[4-(4′-amino-2′-chloro-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (7.1 mg, 0.014 mmol; Preparation 37) was added. The reaction mixture was stirred overnight and then HCTU (8 mg) was added and the reaction mixture was heated to 55° C. After 5 h, the reaction mixture was cooled to RT, ethyl acetate and water were added. The organic layer was concentrated under vacuum and purified by preparative HPLC to provide the di-TFA salt of the title compound (1.3 mg). (m/z): [M+H]+ calcd for C43H51ClN8O5 795.37 found 795.4.

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. temperaturethe reaction mixture was heated to 55° C
  3. waitAfter 5 h
  4. temperaturethe reaction mixture was cooled to RT
  5. concentrationThe organic layer was concentrated under vacuum
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-52a68dc7b3b94e148f2a53b829906228
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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