Diisopropylethylamine → HCID 178502459, compound

HRID 1504345Notes

Reaction equation

HRID 1504345 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:94])[C:75]2[CH:80]=[CH:79][C:78]([N:81]3[CH2:86][CH2:85][N:84]([C:87](=[O:92])[C:88]([CH3:91])([CH3:90])[CH3:89])[CH2:83][C@H:82]3[CH3:93])=[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:54]=[CH:55][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:92])[C:88]([CH3:90])([CH3:91])[CH3:89])[CH2:83][C@H:82]5[CH3:93])=[CH:79][CH:80]=4)=[O:94])=[CH:46][C:47]=3[O:68][C:69]([F:71])([F:72])[F:70])=[CH:51][CH:52]=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 178496717N-{5-chloro-4'-[2-((2S,4S)-4-methoxy-pyrrolidin-2-yl)-1H-imidazol-4-yl]-2-trifluoromethoxy-biphenyl-4-yl}-6-[(R)-4-(2,2-dimethyl-propionyl)-2-methyl-piperazin-1-yl]-nicotinamide tri-HCl

Product 1

HCID 178502459HCID 178502459, compoundYield 68.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of (S)-methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (9.4 mg, 0.046 mmol; Preparation 29) in DMA (1 mL) was added HATU (6.4 mg, 0.017 mmol). The reaction mixture was stirred at RT 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-(2,2-dimethyl-propionyl)-2-methyl-piperazin-1-yl]-nicotinamide tri-HCl (12.0 mg, 0.014 mmol; Preparation 32) was added followed by DIPEA (12.3 μL, 0.07 mmol). The reaction mixture was stirred at RT overnight, concentrated by rotary evaporation, 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, 56% yield). (m/z): [M+H]+ calcd for C46H54ClF3N8O8 939.37. found 939.8.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. concentrationconcentrated by rotary evaporation
  3. dissolutiondissolved in 1:1 acetic acid
  4. customwater (1.5 mL) and purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ea6242f9a8624b80a21763c59d5a70a6
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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