Hydrochloric Acid → HCID 86603650, compound

HRID 226337Notes

Reaction equation

HRID 226337 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:25]=[CH:26]/[C:27](OCC)=[O:28])[CH:5]=[N:6][C:7]=1[NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[O:16])[CH2:11][CH2:10]1.[OH-].[Na+].Cl.ClC1C=C(C=CC(O)=O)C=NC=1NC1CCN(C(=O)NC2C=CC(Cl)=CC=2)CC1.[O:64]1[CH2:69][CH2:68][CH2:67][CH2:66][CH:65]1[O:70][NH2:71].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C1COCC1.CO.CN(C=O)C.CCOC(C)=O.O>[Cl:1][C:2]1[C:7]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=3)=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:5]=[C:4](/[CH:25]=[CH:26]/[C:27](=[O:28])[NH:71][O:70][CH:65]2[CH2:66][CH2:67][CH2:68][CH2:69][O:64]2)[CH:3]=1

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68960254HCID 68960254, compoundHCID 86603649HCID 86603649, compound

Product 1

HCID 86603650HCID 86603650, compoundYield 73.8%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl (2E)-3-{5-chloro-6-[(1-{[(4-chlorophenyl)amino]carbonyl}-4-piperidyl) amino]-3-pyridyl}acrylate (363 mg) in THF (3 ml) and MeOH (3 ml) was added 1N NaOH aq (2.35 ml), the mixture was stirred at 80° C. for 1 hour. The pH of the mixture was adjusted to ca. 4.5 with 1N HCl aq. The solution was evaporated under reduced pressure to give crude 3-{5-Chloro-6-[1-(4-chloro-phenylcarbamoyl)-piperidin-4-ylamino]-pyridin-3-yl}-acrylic acid. To a suspension of crude 3-{5-Chloro-6-[1-(4-chloro-phenylcarbamoyl)-piperidin-4-ylamino]-pyridin-3-yl}-acrylic acid (247 mg) in DMF (3 ml) was added O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (73.1 mg), EDCI (96.9 mg), HOBt (84.3 mg,), the mixture was stirred at 23° C. for 8 hours. The mixed solution was poured into a mixture of water (20 ml) and AcOEt (20 ml). The organic layer was separated, washed with water twice and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 5% MeOH in dichloromethane to give 4-[(3-chloro-5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl}-2-pyridyl)amino]-N-(4-chlorophenyl)-1-piperidinecarboxamide (246 mg).

Workup

  1. customwas evaporated under reduced pressure
  2. customto give crude 3-{5-Chloro-6-[1-(4-chloro-phenylcarbamoyl)-piperidin-4-ylamino]-pyridin-3-yl}-acrylic acid
  3. stirringthe mixture was stirred at 23° C. for 8 hours
  4. customThe organic layer was separated
  5. washwashed with water twice
  6. dry with materialbrine, dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluted with 5% MeOH in dichloromethane

Sources & evidence

ORD record
ord-259a00230b8842f0959063efe237e2d4
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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