Diisopropylethylamine → HCID 178502441, compound

HRID 1504343Notes

Reaction equation

HRID 1504343 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:72][C:73](=[O:93])[C:74]2[CH:79]=[CH:78][C:77]([N:80]3[CH2:85][CH2:84][N:83]([C:86](=[O:91])[C:87]([CH3:90])([CH3:89])[CH3:88])[CH2:82][C@H:81]3[CH3:92])=[N:76][CH:75]=2)=[CH:46][C:47]([O:67][C:68]([F:71])([F:70])[F:69])=[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]([CH3:66])[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]([CH3:66])[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:72][C:73]([C:74]4[CH:75]=[N:76][C:77]([N:80]5[CH2:85][CH2:84][N:83]([C:86](=[O:91])[C:87]([CH3:90])([CH3:89])[CH3:88])[CH2:82][C@H:81]5[CH3:92])=[CH:78][CH:79]=4)=[O:93])=[CH:46][C:47]=3[O:67][C:68]([F:70])([F:71])[F:69])=[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 178461570HCID 178461570, compound

Product 1

HCID 178502441HCID 178502441, compoundYield 37%

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 (5 mL) was added HATU (45.3 mg, 0.12 mmol). The reaction mixture was stirred at RT for 15 min, and N-{5-chloro-4′-[2-((2S,4S)-4-methyl-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 (30.0 mg, 0.036 mmol; Preparation 31 was added followed by DIPEA (86.4 μL, 0.50 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 (14 mg, 37% yield). (m/z): [M+H]+ calcd for C46H54ClF3N8O7 923.38. found 923.8.

Workup

  1. customPreparation 31
  2. additionwas added
  3. stirringThe reaction mixture was stirred at RT overnight
  4. concentrationconcentrated by rotary evaporation
  5. dissolutiondissolved in 1:1 acetic acid
  6. customwater (1.5 mL) and purified by reverse phase HPLC

Sources & evidence

ORD record
ord-6ff64c6c665d4919869b412b12e5b555
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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