Ammonia → (2E)-3-{4-[Cyclohexylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenamide

HRID 229135Notes

Reaction equation

HRID 229135 reaction equation
Cl.C[N:3](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.N.[C:25]1(=[C:31]([C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=2)[C:32]2[CH:37]=[CH:36][C:35](/[CH:38]=[CH:39]/[C:40](O)=[O:41])=[CH:34][CH:33]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:25]1(=[C:31]([C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=2)[C:32]2[CH:37]=[CH:36][C:35](/[CH:38]=[CH:39]/[C:40]([NH2:3])=[O:41])=[CH:34][CH:33]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11267632(2E)-3-{4-[Cyclohexylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoic acid

Product 1

HCID 11256079(2E)-3-{4-[Cyclohexylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent2×

Procedure

To a stirred solution of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.121 g, 0.63 mmol), 1-hydroxybenzotriazole hydrate (0.087 g, 0.644 mmol), 4-dimethylaminopyridine (0.012 g, 0.098 mmol), pyridine (5 mL), and ammonia (0.5 M in 1,4-dioxane) (1.4 mL, 0.7 mmol) was added a solution of (2E)-3-{4-[cyclohexylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoic acid (8) (174 mg, 0.52 mmol) in pyridine (5 mL). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 4 d. The reaction mixture was concentrated and the crude product was partitioned between H2O and CH2Cl2. The organic phase was separated and washed with 1 N HCl (aq.) followed by brine. The organic phase was dried over MgSO4, filtered, and the filtrate was concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 90:10) to give the desired product. The solid was dried under vacuum at 70° C. to give 29 mg (17%) of compound 12 as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.54 (m, 6H), 2.15 (m, 4H), 6.53 (d, J=15.8 Hz, 1H), 6.67 (d, J=8.5 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 7.06 (m, 3H), 7.36 (d, J=15.9 Hz, 1H), 7.45 (d, J=8.2 Hz, 2H), 7.50 (br s, 1H), 9.33 (s, 1). The compound was silated prior to EI analysis. HRMS (EI) Calcd for C25H31NO2Si: 405.2124 (M+.). Found: 405.2126.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe crude product was partitioned between H2O and CH2Cl2
  3. customThe organic phase was separated
  4. washwashed with 1 N HCl (aq.)
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give the crude product
  9. customThe crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 90:10)

Sources & evidence

ORD record
ord-cf85aec2af014ea1aee6149ca27650b8
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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