Ethyl diazoacetate → trans-ethyl 2-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylate

HRID 571413Notes

Reaction equation

HRID 571413 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH:30]=[CH2:31])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[N+](=[CH:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[N-]>C1(C)C=CC=CC=1.C(=O)([O-])O.[Na+].ClCCl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([C@@H:30]3[CH2:31][C@H:34]3[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[N:9][N:10]([C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:4]=2[CH:3]=1.[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([C@H:30]3[CH2:31][C@H:34]3[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[N:9][N:10]([C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:4]=2[CH:3]=1

Participants

7

Reactant 2

HCID 12192Ethyl diazoacetateHCID 1176008446-chloro-1-trityl-3-vinyl-1H-pyrazolo[4,3-c]pyridine

Product 2

HCID 131732820trans-ethyl 2-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylateYield 64%HCID 131732821cis-ethyl 2-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylateYield 31%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-1-trityl-3-vinyl-1H-pyrazolo[4,3-c]pyridine (100 mg, 0.237 mmol, derived from 3a and vinylboronic acid pinacol ester as described in Scheme 1, Step 3) in toluene (2 ml) under nitrogen was treated with ethyl diazoacetate (0.074 ml, 0.711 mmol) and heated at 100° C. overnight to give a yellow solution. The reaction was cooled to room temperature and then diluted with aqueous sodium hydrogen carbonate and dichloromethane. The organic layer was concentrated and purified by column chromatography on silica gel (24 g, eluting with 0-20% EtOAc/hexanes) to give two products: trans-ethyl 2-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylate (77 mg, 64% yield) and cis-ethyl 2-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylate (37 mg, 31% yield). MS ESI calc'd. for C31H26ClIN3O2[M+1]+ 508, found 508.

Workup

  1. customto give a yellow solution
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationThe organic layer was concentrated
  4. custompurified by column chromatography on silica gel (24 g, eluting with 0-20% EtOAc/hexanes)
  5. customto give two products

Sources & evidence

ORD record
ord-5fb82375efbe45048d462df19f1ba535
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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