Triethylamine → methyl 3-(5-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate

HRID 473968Notes

Reaction equation

HRID 473968 reaction equation
[Cl:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=1.[Si:12]([O:19][CH2:20][CH2:21][NH:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])=[N:27][CH:28]=1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].C(N(CC)CC)C>O1CCCC1>[Si:12]([O:19][CH2:20][CH2:21][N:22]([C:23]1[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])=[N:27][CH:28]=1)[C:8]([C:7]1[C:6]([Cl:11])=[N:5][CH:4]=[N:3][C:2]=1[Cl:1])=[O:9])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 121633604,6-Dichloro-pyrimidine-5-carbonyl chlorideHCID 58577899Methyl 3-(5-(2-(tert-butyldimethylsilyloxy)ethylamino)pyridin-2-yloxy)-2,2-dimethylpropanoate

Product 1

HCID 58577890methyl 3-(5-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoateYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4,6-dichloropyrimidine-5-carbonyl chloride (130.5 mg, 0.617 mmol) in anhydrous tetrahydrofuran (1.5 mL) was added dropwise to a solution of methyl 3-(5-(2-(tert-butyldimethylsilyloxy)ethylamino)pyridin-2-yloxy)-2,2-dimethylpropanoate B-18 (157.2 mg, 0.411 mmol) and triethylamine (124.5 mg, 1.233 mmol) in anhydrous tetrahydrofuran (5.0 mL) at 0° C. The reaction mixture was stirred for 30 mins, then allowed to warm to room temperature, stirred for an additional 2 h period and then concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give methyl 3-(5-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)pyridin-2-yloxy)-2,2-dimethylpropanoate B-19 (150 mg, Yield=66%). MS (ESI) [M+1]+ 558.

Workup

  1. customat 0° C
  2. stirringstirred for an additional 2 h period
  3. concentrationconcentrated to dryness under reduced pressure
  4. customThe crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)

Sources & evidence

ORD record
ord-334176d689af4e55b83d0872f9ab108e
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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