Triethylamine → 2-(7-methoxy-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 1898663Notes

Reaction equation

HRID 1898663 reaction equation
[CH:1]1([C@@H:4]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[S:28][C:27]5[C:22](=[N:23][CH:24]=[CH:25][C:26]=5[O:29][CH3:30])[CH:21]=4)[N:18]=3)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:12]=2)=[O:10])[C:5]([OH:7])=O)[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl.[NH:47]1[CH2:50][CH:49]([C:51]#[N:52])[CH2:48]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:51]([CH:49]1[CH2:50][N:47]([C:5](=[O:7])[C@H:4]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[S:28][C:27]5[C:22](=[N:23][CH:24]=[CH:25][C:26]=5[O:29][CH3:30])[CH:21]=4)[N:18]=3)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:36])[CH3:37])[CH:12]=2)=[O:10])[CH:1]2[CH2:2][CH2:3]2)[CH2:48]1)#[N:52]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 45072465Azetidine-3-carbonitrile hydrochlorideHCID 67386740(R)-cyclopropyl-{[2-(7-methoxy-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-acetic acid

Product 1

HCID 673859252-(7-methoxy-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 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-cyclopropyl-{[2-(7-methoxy-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-acetic acid (27 mg, 0.049 mmol) in DMF (2 mL) at room temperature was added triethylamine (34.0 μL, 0.24 mmol), azetidine-3-carbonitrile hydrochloride (6 mg, 0.049 mmol and PyBOP (31 mg, 0.059 mmol). The reaction mixture was stirred for 16 h at the same temperature then poured into EtOAc (25 mL) and washed with water (4×30 mL). The organic phase was dried over Na2SO4 and evaporated under vacuum. The crude residue was purified by column chromatography (SiO2, 23 g, hex:EtOAc, 9:1 to 100% in 30 min) to give 26 mg (64%) of 2-(7-methoxy-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 phase was dried over Na2SO4
  3. customevaporated under vacuum
  4. customThe crude residue was purified by column chromatography (SiO2, 23 g, hex:EtOAc, 9:1 to 100% in 30 min)

Sources & evidence

ORD record
ord-9833bd0f49b0429489b2043df574e554
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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