4-(Chloromethyl)pyridine → Adamantane-1-carboxylic acid(4,5-dimethyl-3-pyridin-4-ylmethyl-3H-thiazol-2-ylidene)-amide

HRID 255103Notes

Reaction equation

HRID 255103 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([NH:8][C:9]([C:11]23[CH2:20][CH:15]4[CH2:16][CH:17]([CH2:19][CH:13]([CH2:14]4)[CH2:12]2)[CH2:18]3)=[O:10])[S:5][C:6]=1[CH3:7].CC(C)([O-])C.[K+].Cl[CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1>CN(C=O)C.C(OCC)(=O)C>[CH3:1][C:2]1[N:3]([CH2:28][C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[C:4](=[N:8][C:9]([C:11]23[CH2:20][CH:15]4[CH2:16][CH:17]([CH2:19][CH:13]([CH2:14]4)[CH2:12]2)[CH2:18]3)=[O:10])[S:5][C:6]=1[CH3:7]

Participants

6

Reactant 3

HCID 745714-(Chloromethyl)pyridineHCID 18128676HCID 18128676, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 24888569Adamantane-1-carboxylic acid(4,5-dimethyl-3-pyridin-4-ylmethyl-3H-thiazol-2-ylidene)-amideYield 36.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
250 °C

Procedure

To a solution of Example 97A (145 mg, 0.50 mmol) in DMF (5 mL) was added potassium tert-butoxide (120 mg, 1.10 mmol) and the hydrochloride salt of 4-chloromethyl-pyridine (82 mg, 0.5 mmol). The mixture was heated in a SmithSynthesizer™ microwave at 250° C. for 15 minutes. The mixture was diluted with ethyl acetate, washed with 1M NaHCO3, and layers were separated. The aqueous layer was extracted with methylene chloride (3×). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was recrystallized from ethyl acetate to afford the title compound (70 mg, 36%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.54-1.72 (m, 6 H), 1.75 (d, J=2.4 Hz, 6 H), 1.91 (s, 3 H), 2.09 (d, J=0.7 Hz, 3 H), 2.17 (d, J=0.7 Hz, 3 H), 5.44 (s, 2 H), 7.06-7.20 (m, 2 H), 8.50-8.56 (m, J=6.1 Hz, 2 H); MS (ESI+) m/z 382 (M+H)+; Anal. Calculated for C22H27N3OS.0.2H2O: C, 68.61; H, 7.17; N, 10.91. Found: C, 68.56; H, 7.12; N, 10.76.

Workup

  1. washwashed with 1M NaHCO3, and layers
  2. customwere separated
  3. extractionThe aqueous layer was extracted with methylene chloride (3×)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-98590140e37e466bacff04407833dda4
Source dataset
uspto-grants-2011_01
Patent number
US07875639B2

Reaction notes

Loading…