Lithium diisopropylamide → HCID 70984495, compound

HRID 928140Notes

Reaction equation

HRID 928140 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.[CH:32]([CH:34]1[CH2:39][CH2:38][CH:37]([C:40]([O:42][CH3:43])=[O:41])[CH2:36][CH2:35]1)=[O:33]>C1COCC1.O.C(OCC)(=O)C>[OH:33][CH:32]([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)[CH:34]1[CH2:35][CH2:36][CH:37]([C:40]([O:42][CH3:43])=[O:41])[CH2:38][CH2:39]1

Participants

7

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 11252253Methyl 4-formylcyclohexane-1-carboxylateHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 70984495HCID 70984495, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
-78 °C

Procedure

A flask containing THF (5 mL) was cooled to −78° C. LDA (1.8 M in THF/heptane/ethylbenzene, 3.3 mL, 5.95 mmol) was added followed by a solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (0.50 g, 1.49 mmol) in THF (5 mL) in one portion and the resulting solution was allowed to stir at −78° C. for thirty minutes. A solution of methyl 4-formylcyclohexanecarboxylate (336 mg, 1.93 mmol) in THF (5 mL) was then added in one portion and the resulting 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 further 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 methyl 4-{hydroxyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}cyclohexanecarboxylate as a mixture of 4 isomers. MS ESI calc'd. for C24H25F3N4O3S [M+H]+ 507. found 507. 1H NMR (500 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.82 (d, J=5.1, 1H), 7.96 (s, 1H), 7.95 (s, 1H), 7.44 (s, 1H), 7.27 (d, J=4.9, 1H), 7.15 (s, 1H), 6.20 (d, J=5.0, 1H), 3.55 (s, 3H), 2.30 (s, 3H), 1.99 (m, 1H), 1.88 (m, 2H), 1.66 (s, 3H), 1.45 (m, 1H), 1.37-1.15 (m, 3H).

Workup

  1. stirringthe resulting 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-9b73cfcda6a74f0691504de5fc713a09
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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