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Trifluoroacetic acid → 6-(2-fluoro-5-((1R)-1-(1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine

HRID 1621878
ノート
印刷プレビュー

反応式

HRID 1621878 の反応式
[CH3:1][O:2][C:3]1[CH:48]=[CH:47][C:6]([CH2:7][N:8]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C@H:23]([N:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]4)[CH3:24])[CH:19]=[N:20][C:21]=3[F:22])[CH:10]=2)=[CH:5][CH:4]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:22][C:21]1[C:16]([C:11]2[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:7][C:6]3[CH:47]=[CH:48][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:38][C:39]3[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=3)[CH:10]=2)=[CH:17][C:18]([C@H:23]([N:25]2[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]2)[CH3:24])=[CH:19][N:20]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 66600507tert-butyl 4-((1R)-1-(5-(6-(bis(4-methoxybenzyl)amino)-2-methyl-4-pyrimidinyl)-6-fluoro-3-pyridinyl)ethyl)-1-piperazinecarboxylate

生成物 1

HCID 685113046-(2-fluoro-5-((1R)-1-(1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine収率 85.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of tert-butyl 4-((1R)-1-(5-(6-(bis(4-methoxybenzyl)amino)-2-methyl-4-pyrimidinyl)-6-fluoro-3-pyridinyl)ethyl)-1-piperazinecarboxylate (0.57 g, 0.87 mmol) in CH2Cl2 (4.3 mL) at 0° C. was treated with TFA (1.29 mL, 17.36 mmol). The reaction mixture was allowed to warm up to RT. After 90 minutes the reaction mixture was concentrated and the residue was dissolved in CH2Cl2 and saturated NaHCO3 (aq.). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give 6-(2-fluoro-5-((1R)-1-(1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.41 g, 0.74 mmol, 85% yield). m/z (ESI, +ve) 557.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.41 (dd, J=9.29, 2.45 Hz, 1H); 8.14-8.18 (m, 1H); 7.18 (d, J=7.43 Hz, 4H); 6.86 (d, J=8.61Hz, 4H); 6.83 (br. s, 1H); 4.74 (br. s., 4H); 3.79 (s, 6H); 3.57 (q, J=6.78 Hz, 1H); 2.96 (m, 4H); 2.62 (s, 3H); 2.57 (br. s., 2H); 2.44-2.51 (m, 2H); 1.40 (d, J=6.85 Hz, 3H).

後処理

  1. concentrationAfter 90 minutes the reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in CH2Cl2
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-f77d0689194d41e4929bdc1dc2ac344b
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08772480B2

反応ノート

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