Methanesulfonyl chloride → Trifluoroacetic acid

HRID 713296Notes

Reaction equation

HRID 713296 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.[CH3:48][S:49](Cl)(=[O:51])=[O:50]>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]([S:49]([CH3:48])(=[O:51])=[O:50])[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 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 131734028HCID 131734028, compound

Product 2

HCID 6422Trifluoroacetic acidYield 207.9%HCID 118159299HCID 118159299, 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 (14.2 μL, 0.081 mmol), and methanesulfonyl chloride (3.2 μL, 0.041 mmol) in DCM (271 μL) was stirred overnight. Purification by HPLC Method A gave the title compound as a TFA salt (6.4 mg) as a white film. 1H NMR (500 MHz, methanol-d4) δ ppm 1.54 (d, J=6.8 Hz, 3H), 1.91-2.02 (m, 2H), 2.07-2.19 (m, 2H), 2.66 (dd, J=16.8, 3.2 Hz, 1H), 2.91 (s, 3H), 2.93-3.06 (m, 3H), 3.34-3.48 (m, 3H), 3.68-3.88 (m, 2H), 3.98 (dd, J=14.2, 6.4 Hz, 1H), 4.45 (dt, J=7.4, 3.8, Hz, 1H), 4.77 (q, J=6.8 Hz, 1H), 5.87-6.21 (m, 1H), 6.82-6.92 (m, 1H), 6.98 (ddd, J=11.4, 8.7, 2.9 Hz, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 518.80.

Workup

  1. customPurification by HPLC Method A

Sources & evidence

ORD record
ord-2553d89a0f724a59972c25ccdfc7d007
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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