Difluoroacetic acid → HCID 118159269, compound

HRID 713290Notes

Reaction equation

HRID 713290 reaction equation
[F:1][CH:2]([F:6])[C:3](O)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[F:47][C:48]1[CH:74]=[C:73]([F:75])[CH:72]=[CH:71][C:49]=1[O:50][CH:51]1[CH2:56][CH2:55][N:54]([C:57]2[N:58]=[C:59]3[CH2:70][CH2:69][NH:68][CH2:67][C:60]3=[N:61][C:62]=2[NH:63][CH:64]([CH3:66])[CH3:65])[CH2:53][CH2:52]1>CC(N(C)C)=O>[F:47][C:48]1[CH:74]=[C:73]([F:75])[CH:72]=[CH:71][C:49]=1[O:50][CH:51]1[CH2:52][CH2:53][N:54]([C:57]2[N:58]=[C:59]3[CH2:70][CH2:69][N:68]([C:3](=[O:4])[CH:2]([F:6])[F:1])[CH2:67][C:60]3=[N:61][C:62]=2[NH:63][CH:64]([CH3:66])[CH3:65])[CH2:55][CH2:56]1

Participants

6

Reactant 4

HCID 9788Difluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1317340252-(4-(2,4-difluorophenoxy)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt

Product 1

HCID 118159269HCID 118159269, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 2,2-difluoroacetic acid (8.2 μL, 0.13 mmol) in DMA (0.4 mL) was treated with HATU (49.6 mg, 0.130 mmol) and DIPEA (45.6 μL, 0.261 mmol). To this was added a solution of 2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (45 mg, 0.087 mmol) in DMA (0.47 mL). The reaction mixture was heated at 60° C. for 50 min. The reaction mixture was allowed to cool to room temperature and was purified directly by HPLC Method B, with the exception that a Phenomenex Gemini® C18, 5 μm, ID 30×75 mm column was used, using a 55% to 90% ACN gradient to give the title compound, as a TFA salt, as a yellow solid (10.0 mg, 19.3%). 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.28 (m, 6H), 1.96 (m, 2H), 2.12 (m, 2H), 2.79 (t, J=5.9 Hz, 0.7H), 2.85 (t, J=5.8 Hz, 1.3H), 3.05 (m, 2H), 3.42 (m, 2H), 3.92 (dt, J=11.3, 5.8 Hz, 2H), 4.15 (m, 1H), 4.48 (m, 1H), 4.65 (s, 2H), 6.56 (m, 1H), 6.88 (m, 1H), 6.98 (ddd, J=11.3, 8.5, 2.9 Hz, 1H), 7.17 (td, J=9.2, 5.3 Hz, 1H); ESI-MS m/z [M+H]+ 482.5.

Workup

  1. temperatureto cool to room temperature
  2. customwas purified directly by HPLC Method B, with the exception that a Phenomenex Gemini® C18, 5 μm, ID 30×75 mm column

Sources & evidence

ORD record
ord-2fc937e3f39a4a16b041f27ebe9eb781
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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