Lithium diisopropylamide → HCID 178451151, 화합물

HRID 928134노트

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HRID 928134 반응식
[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]

참가 물질

7

반응물 3

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

생성물 1

HCID 178451151HCID 178451151, 화합물

시약·촉매·용매 3

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

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=+++

후처리

  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

출처 및 근거

ORD 기록
ord-a5de000777f04a30af7b0a130b9a482c
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290490B2

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