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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 4-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-4-methylcyclohexylcarbamate

HRID 246653
Notes
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Reaction equation

HRID 246653 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](O)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Cl.[NH2:25][C:26]1([CH3:40])[CH2:31][CH2:30][CH:29]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:28][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>[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([CH3:40])[CH2:31][CH2:30][CH:29]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[CH2:28][CH2:27]5)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 71279525Tert-butyl 4-amino-4-methylcyclohexylcarbamate hydrochlorideHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71279681
tert-butyl 4-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-4-methylcyclohexylcarbamate
Yield 49%

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 (0.08 g, 0.26 mmol), tert-butyl 4-amino-4-methylcyclohexylcarbamate hydrochloride (0.07 g, 0.26 mmol), EDCI (0.076 g, 0.4 mmol), DMAP (0.05 g, 0.4 mmol), HOBT (0.054 g, 0.4 mmol) and DIPEA (0.206 g, 1.6 mmol) in 20 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 4-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-4-methylcyclohexylcarbamate (0.065 g, 49%) as a white solid which was used for the next step without further purification. MS: (M+H)+=522.2.

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-f3003fc128cb4aebae4fa89a4a63075f
Source dataset
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08658646B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes