Diisopropylethylamine → HCID 178502460, compound

HRID 1504347Notes

Reaction equation

HRID 1504347 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[C:7]([OH:9])=O)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.Cl.[Cl:43][C:44]1[C:45]([NH:73][C:74](=[O:95])[C:75]2[CH:80]=[CH:79][C:78]([N:81]3[CH2:86][CH2:85][N:84]([C:87](=[O:93])[C:88]([CH3:92])([CH3:91])[CH2:89][OH:90])[CH2:83][C@H:82]3[CH3:94])=[N:77][CH:76]=2)=[CH:46][C:47]([O:68][C:69]([F:72])([F:71])[F:70])=[C:48]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[N:57]=[C:58]([C@@H:61]4[CH2:65][C@H:64]([O:66][CH3:67])[CH2:63][NH:62]4)[NH:59][CH:60]=3)=[CH:52][CH:51]=2)[CH:49]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:1][O:2][C:3](=[O:4])[NH:5][C@@H:6]([CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[C:7]([N:62]1[CH2:63][C@@H:64]([O:66][CH3:67])[CH2:65][C@H:61]1[C:58]1[NH:59][CH:60]=[C:56]([C:53]2[CH:52]=[CH:51][C:50]([C:48]3[CH:49]=[C:44]([Cl:43])[C:45]([NH:73][C:74]([C:75]4[CH:76]=[N:77][C:78]([N:81]5[CH2:86][CH2:85][N:84]([C:87](=[O:93])[C:88]([CH3:91])([CH3:92])[CH2:89][OH:90])[CH2:83][C@H:82]5[CH3:94])=[CH:79][CH:80]=4)=[O:95])=[CH:46][C:47]=3[O:68][C:69]([F:71])([F:72])[F:70])=[CH:55][CH:54]=2)[N:57]=1)=[O:9]

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 59264488(S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 178496718HCID 178496718, compound

Product 1

HCID 178502460HCID 178502460, compoundYield 56.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of (S)-methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (37.6 mg, 0.17 mmol) in DMA (1 mL) was added HATU (65.9 mg, 0.17 mmol). The reaction mixture was stirred for 15 min and N-{5-chloro-4′-[2-((2S,4S)-4-methoxy-pyrrolidin-2-yl)-1H-imidazol-4-yl]-2-trifluoromethoxy-biphenyl-4-yl}-6-[(R)-4-(3-hydroxy-2,2-dimethyl-propionyl)-2-methyl-piperazin-1-yl]-nicotinamide 3HCl (100 mg, 0.12 mmol; Preparation 34) was added followed by DIPEA (0.10 mL, 0.58 mmol) and the reaction mixture was stirred at RT overnight, concentrated by rotary evaporation, dissolved in 1:1 acetic acid:water (4 mL) and purified by reverse phase HPLC. Fractions containing the desired compound were combined and lyophilized to provide the di-TFA salt of the title compound (65.2 mg) as a white powder. Impure fractions were lyophilized, dissolved in 1:1 acetic acid:water (1.5 mL) and purified by reverse phase HPLC to provide additional di-TFA salt of the title compound (75 mg total, 55% yield). (m/z): [M+H]+ calcd for C46H54ClF3N8O9 955.37. found 955.8.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. concentrationconcentrated by rotary evaporation
  3. dissolutiondissolved in 1:1 acetic acid
  4. customwater (4 mL) and purified by reverse phase HPLC
  5. additionFractions containing the desired compound

Sources & evidence

ORD record
ord-a3e835a2c022446b9601d58317383af5
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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