Triethylamine → 2-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide

HRID 446945Notes

Reaction equation

HRID 446945 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[NH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][N:27]([CH3:31])[C:26]1=[O:32].C(N(CC)CC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:31][N:27]1[CH2:28][CH2:29][CH2:30][C@@H:25]([NH:24][C:13]([C:12]2[C:6]3[C:7](=[N:8][CH:9]=[C:4]([CH:1]4[CH2:2][CH2:3]4)[N:5]=3)[N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:21])([CH3:22])[CH3:23])[CH:11]=2)=[O:15])[C:26]1=[O:32]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 57516592(R)-3-Amino-1-methylpiperidin-2-oneHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 673880382-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amideYield 74.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 0.45 mmol) and (R)-3-amino-1-methyl-piperidin-2-one (115 mg, 0.90 mmol) in DMF (2.4 mL) at room temperature was added triethylamine (0.19 mL, 1.35 mmol) and PyBOP (257 mg, 0.50 mmol). The reaction mixture was stirred overnight then diluted with EtOAc (30 mL) and washed with water (4×30 mL). The combined organic extracts were dried (Na2SO4) and evaporated under vacuum. The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 149 mg (74%) of 2-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide as a colorless viscous oil.

Workup

  1. washwashed with water (4×30 mL)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. customevaporated under vacuum
  4. customThe crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)

Sources & evidence

ORD record
ord-3dea49ab27f145379f38a1fa87a9485c
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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