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-methylazetidine-1-carboxylate

HRID 246627Notes

Reaction equation

HRID 246627 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.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[NH2:44][C:45]1([CH3:56])[CH2:48][N:47]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:46]1>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]5([CH3:56])[CH2:48][N:47]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:46]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

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 56924482tert-Butyl 3-amino-3-methylazetidine-1-carboxylateHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280627tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylazetidine-1-carboxylateYield 76.9%

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 (80 mg, 0.26 mmol) and DIEA (83 mg, 0.64 mmol) in 6 mL of DMF were added EDCI (98 mg, 0.51 mmol) and DMAP (88 mg, 0.72 mmol) at room temperature. 20 minutes later, tert-butyl 3-amino-3-methylazetidine-1-carboxylate (95 mg, 0.51 mmol) was added 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 crude tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylazetidine-1-carboxylate (75 mg, 76.9%) as a yellow solid. MS: (M+H)+=480.1.

Workup

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

Sources & evidence

ORD record
ord-e3f50a3307e3449a94dd2c79f42c613b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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