Sodium Iodide → trans-tert-Butyl 3-({cyclopropyl[3-[2-(cyclopropyloxy)ethoxy]-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate

HRID 337699Notes

Reaction equation

HRID 337699 reaction equation
[CH:1]1([N:4]([CH2:28][C:29]2[CH:34]=[C:33]([CH2:35][CH2:36][CH2:37][O:38][CH3:39])[CH:32]=[C:31]([OH:40])[CH:30]=2)[C:5]([C@H:7]2[C@H:12]([C:13]3[CH:18]=[CH:17][N:16]([CH3:19])[C:15](=[O:20])[CH:14]=3)[CH2:11][CH2:10][N:9]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].Cl[CH2:50][CH2:51][O:52][CH:53]1[CH2:55][CH2:54]1>CN(C=O)C>[CH:1]1([N:4]([CH2:28][C:29]2[CH:34]=[C:33]([CH2:35][CH2:36][CH2:37][O:38][CH3:39])[CH:32]=[C:31]([O:40][CH2:50][CH2:51][O:52][CH:53]3[CH2:55][CH2:54]3)[CH:30]=2)[C:5]([C@H:7]2[C@H:12]([C:13]3[CH:18]=[CH:17][N:16]([CH3:19])[C:15](=[O:20])[CH:14]=3)[CH2:11][CH2:10][N:9]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 45789860(2-Chloroethoxy)cyclopropaneHCID 131732048trans-Tert-butyl 3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate

Product 1

HCID 131732047trans-tert-Butyl 3-({cyclopropyl[3-[2-(cyclopropyloxy)ethoxy]-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of trans-tert-butyl 3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate (1.0 eq., Example 92) in DMF (0.1 M) was added cesium carbonate (2 eq.), sodium iodide (0.05 eq.) and (2-chloroethoxy)cyclopropane (3 eq.). The reaction mixture was heated at 100° C. for 22 h. After cooling to RT, the reaction was quenched with sat. aq. ammonium chloride and extracted with EtOAc. The combined organic extracts were washed further with water and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 95:5 (v/v) CH2Cl2:MeOH) afforded the title compound as a colorless oil.

Workup

  1. temperatureAfter cooling to RT
  2. customthe reaction was quenched with sat. aq. ammonium chloride
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed further with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated in vacuo
  8. customPurification of the crude product
  9. customthus obtained by way of flash chromatography (SiO2, 95:5 (v/v) CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-45f975ea3537434da7ba71f23193a770
Source dataset
uspto-grants-2014_11
Patent number
US08889714B2

Reaction notes

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