1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylbutylcarbamate

HRID 246647Notes

Reaction equation

HRID 246647 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=O)=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[NH2:44][C:45]([CH3:57])([CH3:56])[CH2:46][CH2:47][NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52]>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:44][C:45]([CH3:57])([CH3:56])[CH2:46][CH2:47][NH:48][C:49](=[O:55])[O:50][C:51]([CH3:53])([CH3:52])[CH3:54])=[O:23])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 45072486tert-butyl N-(3-amino-3-methylbutyl)carbamateHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280317tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylbutylcarbamateYield 69.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.32 mmol) and DIEA (124 mg, 0.96 mmol) in 6 mL of DMF was added EDCI (123 mg, 0.64 mmol) and DMAP (110 mg, 0.90 mmol) at room temperature followed by tert-butyl 3-amino-3-methylbutylcarbamate (260 mg, 1.28 mmol) in one portion and the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into 40 mL of water, filtered and the filter cake was washed with petroleum ether to give tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylbutylcarbamate (110 mg, 69.4%) as a yellow solid which was used for the next step without further purification. MS: (M+H)+=496.2.

Workup

  1. filtrationfiltered
  2. washthe filter cake was washed with petroleum ether

Sources & evidence

ORD record
ord-fc39a18692604153bac2a1c4dd05d584
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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