Lithium diisopropylamide → HCID 178451151, compound

HRID 928134Notes

Reaction equation

HRID 928134 reaction equation
[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]

Participants

7

Reactant 3

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

Product 1

HCID 178451151HCID 178451151, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

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=+++

Workup

  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

Sources & evidence

ORD record
ord-a5de000777f04a30af7b0a130b9a482c
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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