Diisopropylethylamine → Trifluoroacetic acid

HRID 713350Notes

Reaction equation

HRID 713350 reaction equation
[CH3:1][O:2][C@H:3]([CH3:7])[C:4]([OH:6])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:41][C:42]([C:44]([F:47])([F:46])[F:45])=[O:43].[F:48][CH:49]([F:78])[CH2:50][NH:51][C:52]1[N:53]=[C:54]2[CH2:76][CH:75]([CH3:77])[NH:74][CH2:73][C:55]2=[N:56][C:57]=1[N:58]1[CH2:63][CH2:62][CH:61]([O:64][C:65]2[CH:70]=[CH:69][C:68]([F:71])=[CH:67][C:66]=2[F:72])[CH2:60][CH2:59]1>CN(C=O)C>[F:78][CH:49]([F:48])[CH2:50][NH:51][C:52]1[N:53]=[C:54]2[CH2:76][CH:75]([CH3:77])[N:74]([C:4](=[O:6])[C@H:3]([O:2][CH3:1])[CH3:7])[CH2:73][C:55]2=[N:56][C:57]=1[N:58]1[CH2:59][CH2:60][CH:61]([O:64][C:65]2[CH:70]=[CH:69][C:68]([F:71])=[CH:67][C:66]=2[F:72])[CH2:62][CH2:63]1.[C:42]([OH:43])([C:44]([F:47])([F:46])[F:45])=[O:41]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733584(2R)-2-methoxypropanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131734043N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 243.6%HCID 118159308(2R)-1-(2-(2,2-difluoroethylamino)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7-methyl-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)-2-methoxypropan-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (R)-2-methoxypropanoic acid (1.9 mg, 0.018 mmol), DIPEA (7.0 mg, 0.054 mmol), and HATU (6.9 mg, 0.018 mmol) in DMF (90 μL) was stirred for 10 min at room temperature then treated with N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (10 mg, 0.018 mmol). The resulting reaction mixture was stirred for 2 h. The crude reaction mixture was diluted in DMF, filtered through a hydrophilic PTFE 0.45 μm filter (Millipore® Millex-LCR), and purified via HPLC Method A to give the title compound as a TFA salt (5 mg) as a white solid. 1H NMR (400 MHz, methanol-d4, mixture of rotamers) 6 ppm 1.17 (t, J=6.6 Hz, 1.4H), 1.27 (dd, J=6.7, 2.7 Hz, 1.6H), 1.33 (dd, J=11.6, 6.8 Hz, 1.4H), 1.38 (dd, J=6.7, 2.7 Hz, 1.6H), 1.92-2.03 (m, 2H), 2.09-2.18 (m, 2H), 2.53-2.68 (m, 1H), 2.94-3.05 (m, 2H), 3.08-3.10 (m, 0.5H), 3.12-3.14 (m, 0.5H), 3.35 (s, 3H), 3.37-3.42 (m, 2H), 3.78 (td, J=14.5, 4.2 Hz, 2H), 4.03 (t, J=18.8 Hz, 1H), 4.30-4.41 (m, 1H), 4.43-4.51 (m, 1H), 4.70-4.82 (m, 1H), 5.03-5.14 (m, 0.5H), 5.18-5.23 (m, 0.5H), 5.90-6.22 (m, 1H), 6.85-6.91 (m, 1H), 6.99 (ddd, J=11.3, 8.5, 2.9 Hz, 1H), 7.18 (td, J=9.2, 5.4 Hz, 1H); ESI-MS m/z [M+H]+ 525.9.

Workup

  1. customThe resulting reaction mixture
  2. customThe crude reaction mixture
  3. filtrationfiltered through a hydrophilic PTFE 0.45 μm
  4. filtrationfilter (Millipore® Millex-LCR)
  5. custompurified via HPLC Method A

Sources & evidence

ORD record
ord-9fafcccf36f04e91b850223adec4dd71
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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