Diisopropylethylamine → Trifluoroacetic acid

HRID 713338Notes

Reaction equation

HRID 713338 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[F:8][CH:9]([F:37])[CH2:10][NH:11][C:12]1[N:13]=[C:14]2[CH2:36][CH2:35][NH:34][CH2:33][C:15]2=[N:16][C:17]=1[N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])[CH2:20][CH2:19]1.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.[CH3:71][O:72][C@@H:73]([CH3:77])[C:74](O)=[O:75]>CN(C=O)C>[F:37][CH:9]([F:8])[CH2:10][NH:11][C:12]1[N:13]=[C:14]2[CH2:36][CH2:35][N:34]([C:74](=[O:75])[C@@H:73]([O:72][CH3:71])[CH3:77])[CH2:33][C:15]2=[N:16][C:17]=1[N:18]1[CH2:19][CH2:20][CH:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])[CH2:22][CH2:23]1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 57025662-methoxypropanoic acid, (S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131734031N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 164.4%HCID 118159176(S)-1-(2-(2,2-difluoroethylamino)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)-2-methoxypropan-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (17 mg, 0.032 mmol), HATU (13.2 mg, 0.035 mmol), and DIPEA (12.2 mg, 0.095 mmol) in DMF (158 μL) was stirred for 10 min. Then, (S)-2-methoxypropanoic acid (3.6 mg, 0.035 mmol) was added at room temperature and the resulting reaction mixture stirred overnight. 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 (6 mg) as a clear oil. 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.32 (d, J=6.6 Hz, 1.3H), 1.38 (d, J=6.6 Hz, 1.7H), 1.91-2.02 (m, 2H), 2.09-2.18 (m, 2H), 2.77 (t, J=5.8 Hz, 0.9H), 2.85 (t, J=4.9 Hz, 1.1H), 2.96-3.05 (m, 2H), 3.33 (s, 3H), 3.35-3.43 (m, 2H), 3.78 (td, J=14.5, 4.3 Hz, 2H), 3.84-3.97 (m, 2H), 4.31-4.40 (m, 1H), 4.42-4.49 (m, 1H), 4.59 (m, 0.9H), 4.67 (m, 1.1H), 5.90-6.22 (m, 1H), 6.84-6.91 (m, 1H), 6.98 (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]+ 512.4.

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-2c8b48b5cdf54db6a5c68a732f553b54
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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