4-Hydroxymethylpyridine → Ethyl 3-[{[4-({cyclohexyl[3-methyl-5-(pyridin-4-ylmethoxy)-1-benzofuran-2-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoate

HRID 2091346Notes

Reaction equation

HRID 2091346 reaction equation
[CH:1]1([CH:7]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([N:28]([CH3:36])[CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:27])=[CH:22][CH:21]=2)[C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:37]1[CH:42]=[CH:41][C:40]([CH2:43]O)=[CH:39][CH:38]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH:1]1([CH:7]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]([N:28]([CH3:36])[CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:27])=[CH:24][CH:25]=2)[C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([O:18][CH2:43][C:40]4[CH:41]=[CH:42][N:37]=[CH:38][CH:39]=4)=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 114724-HydroxymethylpyridineHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 66777718HCID 66777718, compound

Product 1

HCID 66777901Ethyl 3-[{[4-({cyclohexyl[3-methyl-5-(pyridin-4-ylmethoxy)-1-benzofuran-2-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoateYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 3-{[(4-{[cyclohexyl(5-hydroxy-3-methyl-1-benzofuran-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate (0.23 g) synthesized in Example A155(1) was dissolved in tetrahydrofuran (5 mL), and 4-pyridinemethanol (62 mg), tributylphosphine (0.21 mL) and 1,1′-(azodicarbonyl)dipiperidine (0.21 g) were added to the solution under ice-cooling. The ice bath was removed, the reaction mixture was stirred at room temperature for 12 hr, then hexane (5 mL) was added to the mixture, and the precipitate was filtered off through celite. Water was added to the filtrate, and the mixture was extracted with ethyl acetate. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio) to give the title object compound (0.18 g, 64%) as a pale-yellow oil.

Workup

  1. temperaturecooling
  2. customThe ice bath was removed
  3. additionhexane (5 mL) was added to the mixture
  4. filtrationthe precipitate was filtered off through celite
  5. additionWater was added to the filtrate
  6. extractionthe mixture was extracted with ethyl acetate
  7. concentrationThe extract was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio)

Sources & evidence

ORD record
ord-c5eac815c4bc4843a9203a7523410f6d
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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