1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl [(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl)-2-pyridinyl)carbamate

HRID 226376Notes

Reaction equation

HRID 226376 reaction equation
[C:1]([O:5][C:6]([N:8]([C@@H:20]1[CH2:24][CH2:23][N:22]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:21]1)[C:9]1[N:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17](O)=[O:18])=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]1[O:37][NH2:38].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH:26]1([CH2:25][N:22]2[CH2:23][CH2:24][C@@H:20]([N:8]([C:9]3[CH:10]=[CH:11][C:12](/[CH:15]=[CH:16]/[C:17](=[O:18])[NH:38][O:37][CH:32]4[CH2:33][CH2:34][CH2:35][CH2:36][O:31]4)=[CH:13][N:14]=3)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:21]2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68959166(2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid

Product 1

HCID 86603680tert-butyl [(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl)-2-pyridinyl)carbamateYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (77 mg, 0.66 mmol), HOBt (89 mg, 0.66 mmol) and EDCI (126 mg, 0.66 mmol) in DMF (4.5 mL) was stirred at 0° C. for 1 hr and the mixture was stirred at ambient temperature for 18 hrs. The reaction mixture was evaporated in vacuo and the residue was partitioned between saturated sodium bicarbonate solution and EtOAc. The organic layer was separated, washed water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by preparative thin layer chromatography (chloroform-MeOH=10-1) to give tert-butyl [(3R)-1-(cyclopentylmethyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl}-2-pyridinyl)carbamate (181 mg, 69%) as an amorphous powder.

Workup

  1. stirringthe mixture was stirred at ambient temperature for 18 hrs
  2. customThe reaction mixture was evaporated in vacuo
  3. customthe residue was partitioned between saturated sodium bicarbonate solution and EtOAc
  4. customThe organic layer was separated
  5. washwashed water and brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by preparative thin layer chromatography (chloroform-MeOH=10-1)

Sources & evidence

ORD record
ord-25ef1e28010e4c65b02a7326904b498b
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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