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-methylcyclobutylcarbamate hydrochloride

HRID 246669Notes

Reaction equation

HRID 246669 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.[ClH:24].[NH2:25][C:26]1([CH3:38])[CH2:29][CH:28]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:27]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C>[ClH:24].[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:25][C:26]5([CH3:38])[CH2:29][CH:28]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:27]5)=[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 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71280568Tert-butyl 3-amino-3-methylcyclobutylcarbamate hydrochloride

Product 1

HCID 71279744tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylcyclobutylcarbamate hydrochlorideYield 69%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.1 g, 0.32 mmol), tert-butyl 3-amino-3-methylcyclobutylcarbamate hydrochloride (0.1 g, 0.42 mmol), EDCI (0.092 g, 0.48 mmol), DMAP (0.059 g, 0.48 mmol), HOBT (0.065 g, 0.48 mmol) and DIPEA (0.248 g, 1.92 mmol) in 25 mL of DMF was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was passed through a pad of silica gel (200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (4:1, v/v) to give tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylcyclobutylcarbamate hydrochloride (0.11 g, 69%) as crude white solid which was used for the next step without further purification. MS: (M+H)+=494.2.

Workup

  1. customThe solvent was removed under reduced pressure
  2. washeluting with a mixture of petroleum ether and ethyl acetate (4:1

Sources & evidence

ORD record
ord-a7e0af0b23b9465eb1d37726c729d7e7
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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