Diisopropylethylamine → Trifluoroacetic acid

HRID 713346

反応式

HRID 713346 の反応式
[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:13]=[C:14]2[CH2:36][CH:35]([CH3:37])[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.FC(F)C(OC(=O)C(F)F)=O.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[F:38][CH:9]([F:8])[CH2:10][NH:11][C:12]1[N:13]=[C:14]2[CH2:36][CH:35]([CH3:37])[N:34]([C:2](=[O:1])[CH:4]([F:7])[F:5])[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]

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 2774048Difluoroacetic anhydrideHCID 131734043N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

生成物 2

HCID 6422Trifluoroacetic acid収率 487.2%HCID 118159241HCID 118159241、化合物

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of N-(2,2-difluoroethyl)-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (10 mg, 0.018 mmol), 2,2-difluoroacetic anhydride (4.7 mg, 0.027 mmol), and DIPEA (7.0 mg, 0.054 mmol) in DCM (90 μL) was stirred at room temperature for 2 h. 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 (5 mg) as a white solid. 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.21 (d, J=7.1 Hz, 1.2H), 1.29 (d, J=6.6 Hz, 1.8H), 1.92-2.03 (m, 2H), 2.09-2.19 (m, 2H), 2.58-2.69 (m, 1H), 2.98-3.07 (m, 2.4H), 3.11-3.17 (m, 0.6H), 3.35-3.44 (m, 2H), 3.78 (td, J=14.5, 4.3 Hz, 2H), 4.11 (d, J=17.2 Hz, 1H), 4.42-4.51 (m, 1H), 4.60-4.67 (m, 0.6H), 4.73-4.77 (m, 0.4H), 5.05 (d, J=17.7 Hz, 0.6H), 5.11-5.18 (m, 0.4H), 5.89-6.22 (m, 1H), 6.39-6.73 (m, 1H), 6.85-6.91 (m, 1H), 6.99 (ddd, J=11.4, 8.6, 3.0 Hz, 1H), 7.18 (td, J=9.3, 5.4 Hz, 1H); ESI-MS m/z [M+H]+ 517.9.

後処理

  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

出典と根拠

ORDレコード
ord-a4a1d2c40c484063b1ec1c4a677b66b6
出典データセット
uspto-grants-2015_11
特許番号
US09181249B2

関連ノート

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