1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2E)-3-(5-chloro-6-([(3R)-1-(3-methylbenzyl)-3-pyrrolidinyl]amino)-3-pyridinyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 226433Notes

Reaction equation

HRID 226433 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:22]=[CH:23]/[C:24](O)=[O:25])[CH:5]=[N:6][C:7]=1[NH:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)[CH2:10]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.CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:22]=[CH:23]/[C:24]([NH:34][O:33][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][O:27]2)=[O:25])[CH:5]=[N:6][C:7]=1[NH:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)[CH2:10]1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68962561(2E)-3-(5-chloro-6-{[(3R)-1-(3-methylbenzyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid

Product 1

HCID 86603736(2E)-3-(5-chloro-6-([(3R)-1-(3-methylbenzyl)-3-pyrrolidinyl]amino)-3-pyridinyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamideYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

A mixture of A mixture of (2E)-3-(5-chloro-6-{[(3R)-1-(3-methylbenzyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid (410 mg), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (142 mg), HOBt (156 mg) and EDCI (180 mg) in DMF (15 ml) was stirred at ambient temperature for 15 hours. The reaction mixture was poured into a mixture of AcOEt-H2O and the organic layer was washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-MeOH (9:1). The eluted fractions containing the desired product were collected and evaporated in vacuo to give (2E)-3-(5-chloro-6-([(3R)-1-(3-methylbenzyl)-3-pyrrolidinyl]amino)-3-pyridinyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (400 mg).

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over MgSO4
  3. customThe solvent was evaporated in vacuo
  4. customthe residue was chromatographed on silicagel
  5. washeluting with AcOEt-MeOH (9:1)
  6. additionThe eluted fractions containing the desired product
  7. customwere collected
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-e19a20e3808c4e9cb18bd849f215374e
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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