1-Hydroxybenzotriazole → (2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 226351Notes

Reaction equation

HRID 226351 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([N:8]2[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]3[N:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22](O)=[O:23])=[CH:16][CH:15]=3)[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[O:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]1[O:33][NH2:34].C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O.CCN=C=NCCCN(C)C.Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]3[N:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([NH:34][O:33][CH:28]4[CH2:29][CH2:30][CH2:31][CH2:32][O:27]4)=[O:23])=[CH:16][CH:15]=3)[CH2:9]2)=[O:7])=[CH:25][CH:26]=1

Participants

7

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68962061(2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)acrylic acid

Product 1

HCID 86603660(2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamideYield 94.4%

Reagents, catalysts & solvents 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)acrylic acid (1.58 g) in DMF (16 mL) was added O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (546 mg), HOBt (744 mg), and EDCI HCl (1.06 mg) and the resulting mixture was stirred at ambient temperature for 4 hours. The reaction mixture was diluted with water and extracted with AcOEt. The organic phase was washed with sat NH4Cl aq solution and sat NaHCO3 aq solution, and brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography eluted with chloroform:methanol=97.5:2.5 to give (2E)-3-(6-{[(3R)-1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-3-pyridyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (1.89 g) as colorless oil.

Workup

  1. extractionextracted with AcOEt
  2. washThe organic phase was washed with sat NH4Cl aq solution
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by silica gel column chromatography
  6. washeluted with chloroform

Sources & evidence

ORD record
ord-260f829c8b2546fe90ef9daccb4a98e6
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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