Diisopropylamine → HCID 71544236, compound

HRID 2205542Notes

Reaction equation

HRID 2205542 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[S:13]1[CH:17]=[CH:16][N:15]=[C:14]1[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([C:26]([F:29])([F:28])[F:27])[CH:19]=1.[C:30]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1)(=[O:32])[CH3:31]>C1COCC1>[OH:32][C:30]([C:17]1[S:13][C:14]([C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([C:26]([F:27])([F:28])[F:29])[CH:19]=2)=[N:15][CH:16]=1)([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1)[CH3:31]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 142824-AcetylpyridineHCID 86680496HCID 86680496, compoundHCID 178418339Butyllithium

Product 1

HCID 71544236HCID 71544236, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of diisopropylamine (0.08 mL, 0.59 mmol) in THF (7 mL) was cooled to −78° C., and 1.6M n-BuLi in hexanes (0.49 mL, 0.78 mmol) added. The reaction mixture was allowed to stir at 0° C. for 30 min, again cooled to −78° C. and a solution of 4-(thiazol-2-yl)-2-(trifluoromethyl) benzonitrile (0.1 g, 0.39 mmol) in THF (2 mL) added dropwise at −78° C. for 30 min 4-Acetyl pyridine (0.048 mL, 0.43 mmol) in THF (2 mL) at −78° C. was then slowly added, the reaction was stirred for 1 hour and quenched with saturated ammonium chloride (2 mL), and water (10 mL). The reaction mixture was extracted with ethyl acetate (20 mL), the organic layer was dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure to obtain crude product. The crude product was product purified by Prep TLC (5% methanol in dichloromethane) to give 4-(5-(1-hydroxy-1-(pyridin-4-yl)ethyl)thiazol-2-yl)-2-(trifluoromethyl)benzonitrile (30 mg, 21%) as pale yellow solid in 99.1% HPLC purity. 1H NMR (400 MHz, DMSO-d6): δ 8.54 (d, 2H), 8.36-8.32 (m, 2H), 8.24 (d, 1H), 8.03 (s, 1H), 7.52-7.51 (m, 2H), 6.81 (s, 1H), 1.97 (s, 3H). LC-MS m/z calculated for [M+H]+376.07. found 375.7.

Workup

  1. temperatureagain cooled to −78° C.
  2. additionwas then slowly added
  3. stirringthe reaction was stirred for 1 hour
  4. customquenched with saturated ammonium chloride (2 mL), and water (10 mL)
  5. extractionThe reaction mixture was extracted with ethyl acetate (20 mL)
  6. dry with materialthe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customto obtain crude product
  10. custompurified by Prep TLC (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e8e0f66ff2fb444697589fdd26d5d81d
Source dataset
uspto-grants-2016_06
Patent number
US09371316B2

Reaction notes

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