Triethylamine → (S)-2-cyclopropyl-N-(1-(dimethylamino)-1-oxopropan-2-yl)-5-((2-(trimethyl-silyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 446950Notes

Reaction equation

HRID 446950 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:15][C@@H:16]([CH3:20])[C:17](O)=[O:18])=[O:14])=[CH:11][N:10]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[CH2:29]([N:31](CC)[CH2:32]C)C.Cl.CNC.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:15][C@@H:16]([CH3:20])[C:17]([N:31]([CH3:32])[CH3:29])=[O:18])=[O:14])=[CH:11][N:10]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:7]3=[N:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 2724699PyBOPHCID 67387896(S)-2-(2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)propanoic acid

Product 1

HCID 67388122(S)-2-cyclopropyl-N-(1-(dimethylamino)-1-oxopropan-2-yl)-5-((2-(trimethyl-silyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-(2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)propanoic acid (253 mg, 0.63 mmol), triethylamine (0.44 mL, 3.13 mmol), and dimethylamine hydrochloride (102 mg, 1.25 mmol) in DMF (5 mL) at room temperature was added PyBOP (358 mg, 0.69 mmol). The reaction mixture was stirred overnight then diluted with EtOAc (50 mL) and washed with water (4×25 mL). The organic extracts were combined and dried (Na2SO4) then evaporated under vacuum. The crude residue was purified by SiO2 chromatography (24 g, hexanes:EtOAc, 3:7) to give 190 mg (70%) of (S)-2-cyclopropyl-N-(1-(dimethylamino)-1-oxopropan-2-yl)-5-((2-(trimethyl-silyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide as a colorless viscous oil.

Workup

  1. washwashed with water (4×25 mL)
  2. dry with materialdried (Na2SO4)
  3. customthen evaporated under vacuum
  4. customThe crude residue was purified by SiO2 chromatography (24 g, hexanes:EtOAc, 3:7)

Sources & evidence

ORD record
ord-28cf7713142e445ab3499359a3504dee
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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