Diethyl Ether → HCID 67359820, compound

HRID 1667202Notes

Reaction equation

HRID 1667202 reaction equation
[O:1]=[C:2]1[C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:20][C:21](O)=[O:22].[F:24][C:25]1[CH:26]=[C:27]([CH:35]=[CH:36][C:37]=1[F:38])[O:28][CH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(N=C=NCCCN(C)C)C.CCOCC>CN(C)C1C=CN=CC=1.C(Cl)Cl>[F:24][C:25]1[CH:26]=[C:27]([CH:35]=[CH:36][C:37]=1[F:38])[O:28][CH:29]1[CH2:34][CH2:33][N:32]([C:21](=[O:22])[CH2:20][N:3]2[CH2:4][CH2:5][CH2:6][C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:2]2=[O:1])[CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 16244268HCID 16244268, compoundHCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acid

Product 1

HCID 67359820HCID 67359820, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of the product of Example 68E (225 mg, 0.73 mmol), 4-(3,4-difluorophenoxy)piperidine (155 mg, 0.73 mmol), and 4-(dimethylamino)pyridine (8.9 mg, 0.07 mmol) in CH2Cl2 (3 mL) at ambient temperature was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.129 mL, 0.727 mmol) via syringe. The reaction was stirred for 18 hours, then diluted with 50 mL CH2Cl2 and washed with 1 N aqueous HCl, saturated aqueous NaHCO3 solution and brine, dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 50% ethyl acetate/hexanes). Hexanes (20 mL) were added and the flask was placed in an ultrasonic bath for 10 minutes resulting in a milky mixture. Ether (6 mL) was added to help precipitate the solid, which was collected by vacuum filtration and air-dried to give the titled compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.15 (m, 10H), 7.06 (dd, J=19.1, 9.1, 1H), 6.72 (ddd, J=11.9, 6.6, 3.0, 1H), 6.64-6.55 (m, 1H), 4.49-4.32 (m, 2H), 4.11 (d, J=15.6, 1H), 3.80-3.33 (m, 6H), 2.73-2.56 (m, 2H), 2.01-1.72 (m, 6H); MS (ESI+) m/z 505 (M+H)+.

Workup

  1. washwashed with 1 N aqueous HCl, saturated aqueous NaHCO3 solution and brine
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 50% ethyl acetate/hexanes)
  6. additionHexanes (20 mL) were added
  7. waitthe flask was placed in an ultrasonic bath for 10 minutes
  8. customresulting in a milky mixture
  9. customto help precipitate the solid, which
  10. filtrationwas collected by vacuum filtration
  11. customair-dried

Sources & evidence

ORD record
ord-260037dc87e44c4b9805bb8a2f1cbda8
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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