Methoxyacetic Acid → Trifluoroacetic acid

HRID 713297Notes

Reaction equation

HRID 713297 reaction equation
[CH3:1][O:2][CH2:3][C:4]([OH:6])=O.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.[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:56]=[C:55]2[CH:57]([CH3:61])[NH:58][CH2:59][CH2:60][C:54]2=[N:53][C:52]=1[N:62]1[CH2:67][CH2:66][CH:65]([O:68][C:69]2[CH:74]=[CH:73][C:72]([F:75])=[CH:71][C:70]=2[F:76])[CH2:64][CH2:63]1>CN(C=O)C.C(Cl)Cl>[F:77][CH:48]([F:47])[CH2:49][NH:50][C:51]1[N:56]=[C:55]2[CH:57]([CH3:61])[N:58]([C:4](=[O:6])[CH2:3][O:2][CH3:1])[CH2:59][CH2:60][C:54]2=[N:53][C:52]=1[N:62]1[CH2:67][CH2:66][CH:65]([O:68][C:69]2[CH:74]=[CH:73][C:72]([F:75])=[CH:71][C:70]=2[F:76])[CH2:64][CH2:63]1.[C:41]([OH:42])([C:43]([F:46])([F:45])[F:44])=[O:40]

Participants

8

Reactant 4

HCID 12251Methoxyacetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131734028HCID 131734028, compound

Product 2

HCID 6422Trifluoroacetic acidYield 240.4%HCID 118159333HCID 118159333, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-methoxyacetic acid (2.4 mg, 0.027 mmol), HATU (10.3 mg, 0.027 mmol), and DIPEA (14.2 μL, 0.081 mmol) in DMF (271 μl) was stirred at room temperature for 10 min. To this was then added N-(2,2-difluoroethyl)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (15 mg, 0.027 mmol) in DCM (271 μL) and the reaction mixture was stirred overnight. Purification by HPLC Method A afforded the title compound as a TFA salt (7.4 mg) as an off-white film. 1H NMR (500 MHz, methanol-d4, mixture of rotamers) δ ppm 1.47 (d, J=6.8 Hz, 2H), 1.58 (d, J=6.8 Hz, 1H), 1.93-2.03 (m, 2H), 2.10-2.18 (m, 2H), 2.63-3.06 (m, 4.1H), 3.12 (td, J=12.9, 3.9 Hz, 0.3H), 3.36-3.51 (m, 5.6H), 3.70-3.88 (m, 2H), 4.02 (dd, J=13.9, 5.6 Hz, 0.7H), 4.18-4.33 (m, 2H), 4.46 (dt, J=7.3, 3.7 Hz, 1H), 4.71 (dd, J=13.4, 5.6 Hz, 0.3H), 4.79-4.84 (m, 0.3H), 5.30 (q, J=6.8 Hz, 0.7H), 5.91-6.21 (m, 1H), 6.85-6.92 (m, 1H), 6.99 (ddd, J=11.3, 8.7, 2.9 Hz, 1H), 7.18 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 512.85.

Workup

  1. customPurification by HPLC Method A

Sources & evidence

ORD record
ord-93aa21691b0446ce9e2f8dc44d246441
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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