Tributylphosphine → 5-(1-Isopropyl-piperidin-4-yloxy)-pyrrolo[2,3-b]pyridine-1,2-dicarboxylic Acid 1-tert-butyl Ester 2-ethyl Ester

HRID 1437707Notes

Reaction equation

HRID 1437707 reaction equation
[CH3:1][CH2:2][O:3][C:4]([C:6]1[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]2=[N:10][CH:11]=[C:12]([OH:14])[CH:13]=[C:8]2[CH:7]=1)=[O:5].[CH:23]([N:26]1[CH2:31][CH2:30][CH:29](O)[CH2:28][CH2:27]1)([CH3:25])[CH3:24].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH3:1][CH2:2][O:3][C:4]([C:6]1[N:15]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[C:9]2=[N:10][CH:11]=[C:12]([O:14][CH:29]3[CH2:30][CH2:31][N:26]([CH:23]([CH3:25])[CH3:24])[CH2:27][CH2:28]3)[CH:13]=[C:8]2[CH:7]=1)=[O:5]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 796811-Isopropylpiperidin-4-olHCID 684243571H-Pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid, 5-hydroxy-, 1-(1,1-dimethylethyl) 2-ethyl ester

Product 1

HCID 684233285-(1-Isopropyl-piperidin-4-yloxy)-pyrrolo[2,3-b]pyridine-1,2-dicarboxylic Acid 1-tert-butyl Ester 2-ethyl EsterYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To the turbid solution of 0.2 g (0.65 mmol) 5-hydroxy-pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (as prepared in WO 05/000849) and 1-isopropyl-piperidin-4-ol (commercially available) in 6 ml tetrahydrofuran, 0.26 g (1.3 mmol) tributylphosphine were added and the mixture was cooled to 0° C. Within 60 min. 32.9 mg (1.3 mmol) 1,1′-(azodicarbonyl)dipiperidine were added under stirring and the reaction was allowed to reach room temperature. After 19 hours the brown suspension was filtered and evaporated. The residue was stirred in tert butyl methyl ether, filtered and the clear filtrate was evaporated and flash-chromatographed on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) to give 60 mg (21%) of the product as a yellow oil.

Workup

  1. customto reach room temperature
  2. filtrationAfter 19 hours the brown suspension was filtered
  3. customevaporated
  4. stirringThe residue was stirred in tert butyl methyl ether
  5. filtrationfiltered
  6. customthe clear filtrate was evaporated
  7. customflash-chromatographed on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v)

Sources & evidence

ORD record
ord-7910e3945a734c7283a50cfbfc0bd7b1
Source dataset
uspto-grants-2009_11
Patent number
US07622466B2

Reaction notes

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