Triethylamine → (S)-tert-butyl 2-(2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)propanoate

HRID 446948Notes

Reaction equation

HRID 446948 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13](O)=[O:14])=[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.C(N(CC)CC)C.Cl.[NH2:32][C@@H:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].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:32][C@@H:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[O:14])=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:23])[CH3:21])[C:7]3=[N:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 11275390tert-Butyl alaninate hydrochlorideHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 67388507(S)-tert-butyl 2-(2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)propanoateYield 85%

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 (250 mg, 0.75 mmol) in DMF (6 mL) at room temperature was added triethylamine (0.52 mL, 3.75 mmol), (S)-tert-butyl 2-aminopropanoate hydrochloride (136 mg, 0.75 mmol) and PyBOP (429 mg, 0.83 mmol). The reaction mixture was stirred overnight then poured into EtOAc (50 mL) and washed with water (4×30 mL). The organic extracts were combined, dried (Na2SO4) and evaporated under reduced pressure. The crude residue was purified by SiO2 column chromatography (12 g, hexanes/EtOAc, 7:3 to 1:1) to give 285 mg (85%) of (S)-tert-butyl 2-(2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)propanoate as a viscous oil.

Workup

  1. washwashed with water (4×30 mL)
  2. dry with materialdried (Na2SO4)
  3. customevaporated under reduced pressure
  4. customThe crude residue was purified by SiO2 column chromatography (12 g, hexanes/EtOAc, 7:3 to 1:1)

Sources & evidence

ORD record
ord-a9414e5f1ed7439dac12e250c0318b6b
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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