Lithium Hexamethyldisilazide → HCID 60154997、化合物

HRID 1811783ノート

反応式

HRID 1811783 の反応式
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][CH:12]=[C:13]2[NH2:16])=[N:8]1.F[C:18]1[C:23]([C:24]2[N:32]=[CH:31][N:30]=[C:29]3[C:25]=2[N:26]=[CH:27][N:28]3[CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[CH:22][CH:21]=[CH:20][N:19]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][CH:12]=[C:13]2[NH:16][C:18]2[C:23]([C:24]3[N:32]=[CH:31][N:30]=[C:29]4[C:25]=3[N:26]=[CH:27][N:28]4[CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:8]1

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 444791786-(2-Fluoropyridin-3-YL)-9-(tetrahydro-2H-pyran-2-YL)-9H-purineHCID 601548222-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

生成物 1

HCID 60154997HCID 60154997、化合物収率 42.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of 2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (37.4 mg, 172 μmol) and 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (51.5 mg, 172 μmol) in THF (1.0 mL) was cooled in an ice bath and treated dropwise with LHMDS (0.55 mL of a 1.0 M solution in THF, 3 equiv.). A deep red solution was obtained. The mixture was stirred for 60 min and then quenched with water (0.050 mL). The mixture was extracted with EtOAc from saturated aqueous NaHCO3, dried (MgSO4) and concentrated to give a dark residue. 2-(Tetrahydro-2H-pyran-2-yl)-N-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-2H-indazol-4-amine (36.6 mg, 42.8% yield) was obtained by flash chromatography on silica (50% EtOAc/hexane) (yellow band on column) as a yellow oil which crystallized upon standing. 1H NMR (400 MHz, CDCl3) δ 12.75 (br. s., 1H); 9.77 (d, J=7.82 Hz, 1H); 9.12 (s, 1H); 8.44 (d, J=3.52 Hz, 1H); 8.38 (s, 2H); 8.06 (d, J=7.04 Hz, 1H); 7.41 (d, 1H); 7.35 (d, J=7.63 Hz, 1H); 6.92-7.03 (m, 1H); 5.88 (d, 1H); 5.73 (d, 1H); 4.13-4.30 (m, 2H); 3.84 (br. s., 2H); 2.17-2.35 (m, 3H); 2.00-2.16 (m, 3H); 1.79 (br. s., 6H). m/z (API-ES) 497.1 (M+H)+.

後処理

  1. customA deep red solution was obtained
  2. customquenched with water (0.050 mL)
  3. extractionThe mixture was extracted with EtOAc from saturated aqueous NaHCO3
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give a dark residue

出典と根拠

ORDレコード
ord-cdf533ffb92b48789fffe092b445260a
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

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