Acetic Anhydride → Trifluoroacetic acid

HRID 713295Notes

Reaction equation

HRID 713295 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[F:8][CH:9]([F:38])[CH2:10][NH:11][C:12]1[N:17]=[C:16]2[CH:18]([CH3:22])[NH:19][CH2:20][CH2:21][C:15]2=[N:14][C:13]=1[N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[CH2:25][CH2:24]1.CCN(C(C)C)C(C)C.C(OC(=O)C)(=O)C>C(Cl)Cl>[F:38][CH:9]([F:8])[CH2:10][NH:11][C:12]1[N:17]=[C:16]2[CH:18]([CH3:22])[N:19]([C:2](=[O:1])[CH3:4])[CH2:20][CH2:21][C:15]2=[N:14][C:13]=1[N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[CH2:25][CH2:24]1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 131734028HCID 131734028, compound

Product 2

HCID 6422Trifluoroacetic acidYield 578.2%HCID 118159119HCID 118159119, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 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), DIPEA (14.20 μL, 0.081 mmol), and acetic anhydride (3.8 μL, 0.041 mmol) in DCM (271 μL) was stirred at room temperature overnight. Purification by HPLC Method A gave the title compound as a TFA salt (8.9 mg) as an off-white film. 1H NMR (500 MHz, methanol-d4, mixture of rotamers) δ ppm 1.45 (d, J=6.8 Hz, 1.9H), 1.58 (d, J=6.8 Hz, 1.1H), 1.93-2.02 (m, 2H), 2.14 (dd, J=12.7, 3.4 Hz, 2H), 2.19-2.23 (m, 3H), 2.62-2.83 (m, 1.5H), 2.87-3.08 (m, 3.2H), 3.35-3.43 (m, 2H), 3.48-3.55 (m, 0.7H), 3.78 (sxtd, J=14.4, 4.2 Hz, 2H), 4.06 (dd, J=14.2, 5.4 Hz, 0.6H), 4.46 (dt, J=7.6, 3.5, Hz, 1H), 4.73 (dd, J=13.2, 5.4 Hz, 0.4H), 5.34 (q, J=6.8 Hz, 0.6H), 5.92-5.97 (m, 1H), 6.06 (dt, J=9.0, 4.3, Hz, 1H), 6.15-6.20 (m, 1H), 6.86-6.91 (m, 1H), 6.99 (ddd, J=11.2, 8.5, 3.2 Hz, 1H), 7.18 (td, J=9.3, 5.4 Hz, 1H); ESI-MS m/z [M+H]+ 482.

Workup

  1. customPurification by HPLC Method A

Sources & evidence

ORD record
ord-9b0f06734b62405d824c3458ef431fe2
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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