Diisopropylethylamine → HCID 178502439, compound

HRID 1504339Notes

Reaction equation

HRID 1504339 reaction equation
OC([C:4]([F:7])([F:6])[F:5])=O.[CH3:8][O:9][C:10]([NH:12][C@@H:13]([CH:47]([CH3:49])[CH3:48])[C:14]([N:16]1[CH2:20][C@@H:19]([CH3:21])[CH2:18][C@H:17]1[C:22]1[NH:23][CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][C:36]([C:39](O)=[O:40])=[CH:35][C:34]=3[O:42]C(F)(F)F)=[CH:29][CH:28]=2)[N:26]=1)=[O:15])=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:74][C:75]1[CH:76]=[CH:77][C:78]([N:81]2[CH2:86][CH2:85][N:84]([C:87]([C@H:89]3[CH2:91][C:90]3([CH3:93])[CH3:92])=[O:88])[CH2:83][C@H:82]2[CH3:94])=[N:79][CH:80]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:8][O:9][C:10](=[O:11])[NH:12][C@H:13]([C:14]([N:16]1[CH2:20][C@@H:19]([CH3:21])[CH2:18][C@H:17]1[C:22]1[NH:23][CH:24]=[C:25]([C:27]2[CH:28]=[CH:29][C:30]([C:33]3[CH:38]=[CH:37][C:36]([C:39](=[O:40])[NH:74][C:75]4[CH:80]=[N:79][C:78]([N:81]5[CH2:86][CH2:85][N:84]([C:87]([C@H:89]6[CH2:91][C:90]6([CH3:93])[CH3:92])=[O:88])[CH2:83][C@H:82]5[CH3:94])=[CH:77][CH:76]=4)=[CH:35][C:34]=3[O:42][C:4]([F:5])([F:6])[F:7])=[CH:31][CH:32]=2)[N:26]=1)=[O:15])[CH:47]([CH3:48])[CH3:49]

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 89541542HCID 89541542, compoundHCID 178502440HCID 178502440, compound

Product 1

HCID 178502439HCID 178502439, compoundYield 65.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4′-{2-[(2S,4S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-4-methyl-pyrrolidin-2-yl]-1H-imidazol-4-yl}-2-trifluoromethoxy-biphenyl-4-carboxylic acid TFA (11.4 mg, 0.016 mmol) and HATU (6.8 mg, 0.018 mmol) in DMF (0.5 mL) at RT was added [(R)-4-(5-amino-pyridin-2-yl)-3-methyl-piperazin-1-yl]-((S)-2,2-dimethyl-cyclopropyl)-methanone (5.1 mg, 0.018 mmol, Preparation 17) followed by N,N-diisopropylethylamine (14.07 μL, 0.081 mmol). 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 di-TFA salt of the title compound (9 mg). (m/z): [M+H]+ calcd for C45H53F3N8O6 859.40. found 859.4.

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-4a924745bb934482b990163cc33e0ee1
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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