Lithium diisopropylamide → HCID 178451151、化合物

HRID 928134ノート

反応式

HRID 928134 の反応式
[Li+].CC([N-]C(C)C)C.[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.[C:32]([C@H:35]1[CH2:40][CH2:39][C@H:38]([C:41]([O:43][CH2:44][CH2:45][CH2:46][CH3:47])=[O:42])[CH2:37][CH2:36]1)(=[O:34])[CH3:33]>C1COCC1.O.C(OCC)(=O)C>[OH:34][C:32]([C@H:35]1[CH2:40][CH2:39][C@H:38]([C:41]([O:43][CH2:44][CH2:45][CH2:46][CH3:47])=[O:42])[CH2:37][CH2:36]1)([C:19]1[S:20][C:16]([C:14]2[CH:13]=[C:12]([NH:21][C:22]3[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=3)[CH:11]=[C:10]([CH3:9])[CH:15]=2)=[CH:17][N:18]=1)[CH3:33]

参加物

7

反応物 3

HCID 2724682Lithium diisopropylamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amineHCID 178451155HCID 178451155、化合物

生成物 1

HCID 178451151HCID 178451151、化合物

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

A flask containing THF (78 mL) was cooled to −78° C. LDA (1.8 M in THF/heptane/ethylbenzene, 21.7 mL, 39.1 mmol) was added followed by a solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (2.63 g, 7.82 mmol) in THF (25 mL). The resulting solution was allowed to stir at −78° C. for thirty minutes. A solution of butyl trans-4-acetylcyclohexanecarboxylate (2.65 g, 11.73 mmol) in THF (10 mL) was added in one portion and the solution was stirred for 1 hour at −78° C. The reaction was then diluted with water and allowed to warm to room temperature. The mixture was then diluted with water and ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford racemic butyl trans-4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate. MS ESI calc'd. for C28H34F3N4O3S [M+H]+ 563. found 563. 1H NMR (500 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.83 (d, J=4.9, 1H), 7.98-7.91 (m, 2H), 7.45 (s, 1H), 7.27 (d, J=4.9, 1H), 7.14 (s, 1H), 5.84 (s, 1H), 3.96 (t, J=6.5, 2H), 2.31 (s, 3H), 2.16-2.06 (m, 1H), 1.99-1.79 (m, 2H), 1.64 (s, 1H), 1.58-1.44 (m, 6H), 1.32-1.18 (m, 6H), 1.04 (d, J=13.1, 1H), 0.85 (t, J=7.4, 3H). rhSyk=+++

後処理

  1. stirringthe solution was stirred for 1 hour at −78° C
  2. temperatureto warm to room temperature
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on silica gel

出典と根拠

ORDレコード
ord-a5de000777f04a30af7b0a130b9a482c
出典データセット
uspto-grants-2016_03
特許番号
US09290490B2

反応ノート

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