Ethyl Acetate → 2-(7-chloro-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898657Notes

Reaction equation

HRID 1898657 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21](Br)[N:22]=3)[N:17]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].[Cl:34][C:35]1[CH:40]=[CH:39][N:38]=[C:37]2[CH:41]=[C:42]([Sn](CCCC)(CCCC)CCCC)[S:43][C:36]=12.CCOC(C)=O>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:42]4[S:43][C:36]5[C:37](=[N:38][CH:39]=[CH:40][C:35]=5[Cl:34])[CH:41]=4)[N:22]=3)[N:17]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 575166587-Chloro-2-(tributylstannyl)thieno[3,2-b]pyridineHCID 58438590HCID 58438590, compound

Product 1

HCID 584385872-(7-chloro-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amideYield 85.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (180 mg, 0.34 mmol) and 7-chloro-2-tributylstannanyl-thieno[3,2-b]pyridine (162 mg, 0.35 mmol) in DMF (3 mL) were added copper(I) iodide (13.5 mg, 0.071 mmol) and tetrakis(triphenylphosphine)palladium(0) (20.4 mg, 0.018 mmol) under argon atmosphere. The reaction mixture was stirred for 16 h at 90° C. then poured into EtOAc (25 mL) and washed with water (4×30 mL). The organic extracts were dried over Na2SO4 and evaporated under vacuum. The crude residue was purified by column chromatography (SiO2, 11 g, CH2Cl2 100% to CH2Cl2:EtOAc 4:6 in 25 min) to afford 180 mg (82%) of 2-(7-chloro-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

Workup

  1. washwashed with water (4×30 mL)
  2. dry with materialThe organic extracts were dried over Na2SO4
  3. customevaporated under vacuum
  4. customThe crude residue was purified by column chromatography (SiO2, 11 g, CH2Cl2 100% to CH2Cl2:EtOAc 4:6 in 25 min)

Sources & evidence

ORD record
ord-286242d36a9f48e8a21a1a721b7e49f4
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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