Acetic Anhydride → Trifluoroacetic acid

HRID 713331Notes

Reaction equation

HRID 713331 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[C:8]([NH:12][C:13]1[N:14]=[C:15]2[CH2:37][CH2:36][NH:35][CH2:34][C:16]2=[N:17][C:18]=1[N:19]1[CH2:24][CH2:23][CH:22]([O:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[F:33])[CH2:21][CH2:20]1)([CH3:11])([CH3:10])[CH3:9].C(OC(=O)C)(=O)C.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[C:8]([NH:12][C:13]1[N:14]=[C:15]2[CH2:37][CH2:36][N:35]([C:2](=[O:1])[CH3:4])[CH2:34][C:16]2=[N:17][C:18]=1[N:19]1[CH2:20][CH2:21][CH:22]([O:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[F:33])[CH2:23][CH2:24]1)([CH3:11])([CH3:9])[CH3:10].[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

7

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 131734039HCID 131734039, compound

Product 2

HCID 6422Trifluoroacetic acidYield 877%HCID 118159200HCID 118159200, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of N-(tert-butyl)-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (16 mg, 0.030 mmol), acetic anhydride (5.7 μL, 0.060 mmol), and DIPEA (15.8 μL, 0.090 mmol) in DCM (151 μL) was stirred at room temperature 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 (15 mg) as a clear oil. 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.48 (s, 9H), 1.87-1.98 (m, 2H), 2.07-2.17 (m, 2H), 2.19 (s, 1.3H), 2.21 (s, 1.7H), 2.74 (t, J=5.9 Hz, 0.9H), 2.84 (t, J=5.9 Hz, 1.1H), 2.97 (ddd, J=12.4, 8.6, 3.3 Hz, 2H), 3.33-3.37 (m, 2H), 3.80 (t, J=5.9 Hz, 1.1H), 3.85 (t, J=5.9 Hz, 0.9H), 4.43-4.51 (m, 1H), 4.53 (d, J=1.3 Hz, 2H), 6.88 (ddddd, J=9.1, 8.1, 2.9, 1.9, 0.8 Hz, 1H), 6.95-7.02 (m, 1H), 7.18 (td, J=9.2, 5.3 Hz, 1H); ESI-MS m/z [M+H]+ 460.4.

Workup

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

Sources & evidence

ORD record
ord-d8b2ed4840b64a00921d163a6ae21608
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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