Cyclopropanecarboxylic acid → Trifluoroacetic acid

HRID 713351Notes

Reaction equation

HRID 713351 reaction equation
[CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.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:40][C:41]([C:43]([F:46])([F:45])[F:44])=[O:42].[F:47][CH:48]([F:77])[CH2:49][NH:50][C:51]1[N:52]=[C:53]2[CH2:75][CH:74]([CH3:76])[NH:73][CH2:72][C:54]2=[N:55][C:56]=1[N:57]1[CH2:62][CH2:61][CH:60]([O:63][C:64]2[CH:69]=[CH:68][C:67]([F:70])=[CH:66][C:65]=2[F:71])[CH2:59][CH2:58]1>CN(C=O)C>[CH:1]1([C:4]([N:73]2[CH:74]([CH3:76])[CH2:75][C:53]3[C:54](=[N:55][C:56]([N:57]4[CH2:62][CH2:61][CH:60]([O:63][C:64]5[CH:69]=[CH:68][C:67]([F:70])=[CH:66][C:65]=5[F:71])[CH2:59][CH2:58]4)=[C:51]([NH:50][CH2:49][CH:48]([F:77])[F:47])[N:52]=3)[CH2:72]2)=[O:6])[CH2:3][CH2:2]1.[C:41]([OH:42])([C:43]([F:46])([F:45])[F:44])=[O:40]

Participants

7

Reactant 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 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 118159159HCID 118159159, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of cyclopropanecarboxylic acid (1.6 mg, 0.018 mmol), DIPEA (7.0 mg, 0.054 mmol), and HATU (6.9 mg, 0.018 mmol) in DMF (181 μL) was stirred at room temperature for 10 min followed by the addition of 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 0.80-1.01 (m, 4H), 1.13 (d, J=6.6 Hz, 1.4H), 1.27 (d, J=6.3 Hz, 1.6H), 1.91-2.04 (m, 2H), 2.06-2.20 (m, 2H), 2.56-2.60 (m, 0.5H), 2.66-2.70 (m, 0.5H), 3.02 (br s, 2H), 3.13-3.15 (m, 0.5H), 3.16-3.20 (m, 0.5H), 3.34-3.46 (m, 2H), 3.72-3.87 (m, 2H), 4.04 (d, J=18.2 Hz, 1H), 4.41-4.58 (m, 2H), 5.02 (d, J=17.4 Hz, 1.4H), 5.15-5.19 (m, 0.6H), 5.90-6.23 (m, 1H), 6.84-6.91 (m, 1H), 6.99 (ddd, J=11.4, 8.6, 3.0 Hz, 1H), 7.18 (td, J=9.2, 5.3 Hz, 1H); ESI-MS m/z [M+H]+ 507.9.

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-fa7874b57cc340568074e7112eae839d
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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